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The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease. ; European Innovation Partnership ; Montpellier Univ Hosp, Montpellier, France ; European Innovat Partnership Act & Hlth Ageing Re, MAlad Chron Vleillissement Actif France, MACVIA France, Montpellier, France ; INSERM, Ageing & Chron Dis Epidemiol & Publ Hlth Approach, U1168, F-94800 Villejuif, France ; Katholieke Univ Leuven, Dept Microbiol & Immunol, Clin Immunol Lab, Louvain, Belgium ; Transylvania Univ Brasov, Brasov, Romania ; Ghent Univ Hosp, ENT Dept, Upper Airways Res Lab, Ghent, Belgium ; Charite, Dept Dermatol & Allergy, Allergy Ctr Charite, Berlin, Germany ; Global Allergy & Asthma European Network, Berlin, Germany ; iQ4U Consultants Ltd, London, England ; Odense Univ Hosp, Dept Dermatol, Odense, Denmark ; Odense Univ Hosp, Allergy Ctr, Odense, Denmark ; Univ Sydney & Sydney Local Hlth Dist, Woolcock Inst Med Res, Glebe, NSW, Australia ; Hosp City Hlth & Sci Torino, Univ Pneumol Unit AOU Molinette, Turin, Italy ; Montpellier Univ Hosp, Dept Resp Dis, Montpellier, France ; Univ Fed Minas Gerais, Dept Pediat, Sch Med, Belo Horizonte, MG, Brazil ; Humanitas Univ, Asthma & Allergy Clin, Milan, Italy ; Univ S Florida, Div Allergy Immunol, Tampa, FL USA ; Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands ; Univ Fed Bahia, ProAR Nucleo Excelencia Asma, Salvador, BA, Brazil ; GARD Execut Comm, Salvador, BA, Brazil ; EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium ; INSERM, EPAR U707, Paris, France ; Univ Paris 06, EPAR UMR S UPMC, Paris, France ; Suresnes Univ Versailles, Hop Foch, Lab Pharmacol Resp UPRES EA220, St Quentin en Yvelines, France ; Univ Porto, Ctr Res Hlth Technol & Informat Syst CINTESIS, Oporto, Portugal ; Inst CUF Porto, Allergy Unit, Oporto, Portugal ; Hosp CUF Porto, Oporto, Portugal ; Univ Porto, Fac Med, Hlth Informat & Decis Sci Dept CIDES, Rua Dr Placido da Costa S-N, P-4200450 Oporto, Portugal ; Acad Med Ctr, Dept Otorhinolaryngol, Amsterdam, Netherlands ; Erasmus Univ, Inst Hlth Policy & Management IBMG, Rotterdam, Netherlands ; Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland ; Univ Naples Federico II, Hosp Naples R&D & DISMET, Naples, Italy ; Univ Paris 06, UPMC,Equipe EPAR, Sorbonne Univ,Dept Allergol,Inst Pierre Louis Epi, Hopital Enfants Armand Trousseau,AP HP,Ctr Asthme, F-75013 Paris, France ; Charite, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany ; Univ Wurzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany ; Ctr Rhinol & Allergol, Wiesbaden, Germany ; Med Univ Lodz, Barlicki Univ Hosp, Div Internal Med Asthma & Allergy, Lodz, Poland ; Univ Barcelona, CIBERES, IDIBAPS, Hosp Clin,ENT Dept,Clin & Expt Resp Immunoallergy, M Barcelona, Catalonia, Spain ; Univ Chicago, Med Ctr, Sect Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA ; Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA ; Monash Univ, Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia ; Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia ; Monash Univ, Dept Immunol, Melbourne, Vic, Australia ; Univ Manchester, Royal Manchester Childrens Hosp, Inst Human Dev, Ctr Pediat & Child Hlth, Manchester, Lancs, England ; Univ Athens, Athens Gen Childrens Hosp P&A Kyriakou, Pediat Clin 2, Dept Allergy, Athens, Greece ; Nippon Med Sch, Dept Pediat, Tokyo, Japan ; Univ Cape Town, Lung Inst, Allergy Diagnost & Clin Res Unit, Cape Town, South Africa ; Woodbrook Med Ctr, Loughborough, Leics, England ; Univ Edinburgh, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland ; Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland ; McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada ; Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland ; Univ Manitoba, Fac Med, Dept Immunol, Dept Pediat & Child Hlth, Winnipeg, MB, Canada ; Univ Salerno, Div Allergy & Clin Immunol, Salerno, Italy ; Univ Coimbra, Fac Med, Ctr Pneumol, Coimbra, Portugal ; Med Univ Graz, Dept ENT, Graz, Austria ; Vilnius Univ, Fac Med, Clin Childrens Dis, Vilnius, Lithuania ; Vilnius Univ, Inst Publ Hlth, Vilnius, Lithuania ; European Acad Paediat EAP UEMS SP, Brussels, Belgium ; Univ Turku, Dept Lung Dis & Clin Allergol, Turku, Finland ; Terveystalo, Allergy Clin, Turku, Finland ; Univ Bari, Sch Med, Unit Geriatr Immunoallergol, Bari, Italy ; Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden ; Karolinska Inst, Inst Environm Med, Stockholm, Sweden ; Queens Univ, Belfast, Antrim, North Ireland ; Celal Bayar Univ, Dept Pulmonol, Manisa, Turkey ; Med Univ Graz, Dept Dermatol, Graz, Austria ; Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland ; Hosp Quiron Bizkaia, Dept Allergy & Immunol, Erandio, Spain ; Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain ; IMIM Hosp Mar Res Inst, Barcelona, Spain ; CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain ; Univ Pompeu Fabra, Barcelona, Spain ; Kyomed, Montpellier, France ; Karolinska Inst, Dept Med Solna, Clin Immunol & Allergy Unit, Stockholm, Sweden ; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Pediat Pulmonol & Allergy, Stockholm, Sweden ; David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England ; Reg Puglia, Bari, Italy ; Portuguese Natl Programme Resp Dis PNDR, Fac Med Lisbon, Lisbon, Portugal ; Univ Palermo, Dept Internal Med DIBIMIS, Geriatr Unit, Palermo, Italy ; Univ Cape Town, Dept Med, Cape Town, South Africa ; Univ Modena & Reggio Emilia, Dept Oncol Haematol & Resp Dis, Sect Resp Dis, Modena, Italy ; Univ Amsterdam, Acad Med Ctr, Dept Resp Med, Amsterdam, Netherlands ; Natl Inst Dis Chest & Hosp, Dept Resp Med, Dhaka, Bangladesh ; Linkoping Univ, Fac Med, Dept Pediat, Ctr Individualized Med, S-58185 Linkoping, Sweden ; Univ Bonn, Dept Dermatol & Allergy, Bonn, Germany ; Univ Hosp, Dept Resp Med & Allergol, Lund, Sweden ; Montpellier Univ Hosp, Dept Geriatr, BLAIN Montpellier, France ; Univ Montpellier, Euromov, EA 2991, Montpellier, France ; Univ Milan, IRCCS Fdn CaGranda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat, Milan, Italy ; Univ Verona Hosp, Dept Pediat, Verona, Italy ; Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Rome, Italy ; Univ Naples 2, Naples, Italy ; Italian Natl Res Council, Inst Translat Med, Naples, Italy ; Univ Laval, Quebec Heart & Lung Inst, Quebec City, PQ, Canada ; Univ Glasgow, Inst Hlth & Wellbeing, Hlth Econ & Hlth Technol Assessment, Glasgow, Lanark, Scotland ; Univ Hosp Leicester NHS Trust, Inst Lung Hlth, Resp Biomed Unit, Leicester, Leics, England ; Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England ; Johannes Gutenberg Univ Mainz, Univ Med, Mainz, Germany ; Univ Med & Farm Timisoara, Timisoara, Romania ; Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp NHS, London, England ; Ctr Med Docente Trinidad, Caracas, Venezuela ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England ; Reg Languedoc Roussillon, Montpellier, France ; Hosp Valle De Hebron, S Allergol S Med Interna, Barcelona, Spain ; CEDOC, Resp Res Grp, Nova Med Sch, Lisbon, Portugal ; Ctr Hosp Lisboa Cent, EPE, Serv Imunoalergol, Lisbon, Portugal ; Reg Minist Hlth Andalusia, Seville, Spain ; Oslo Univ Hosp, Dept Paediat, Oslo, Norway ; Univ Oslo, Oslo, Norway ; Allergy & Asthma Associates Southern Calif, Mission Viejo, CA USA ; Metropolitan Univ, Univ Simon Bolivar, Allergy & Immunol Lab, Barranquilla, Colombia ; SLaai Sociedad Latinoamer Allergia Asma & Immunol, Cartagena, Colombia ; Gerontopole Toulouse, F-31059 Toulouse, France ; Univ Crete, Fac Med, Dept Social Med, Iraklion, NE, Greece ; Univ CEU San Pablo, Sch Med, Madrid, Spain ; Grigol Robakidze Univ, David Tvildiani Med Univ, AIETI Med Sch, Chachava Clin, Tbilisi, Rep of Georgia ; Pulmonolory Res Inst FMBA, Moscow, Russia ; GARD Execut Comm, Moscow, Russia ; IRCCS Azienda Osped Univ San Martino, Dept Med, Genoa, Italy ; Univ Minho, Sch Hlth Sci, Res Inst ICVS, ICVS 3BsPT Govt Associate Lab,Life & Hlth Sci, Braga, Portugal ; Nova Southeastern Univ, Dept Med, Davie, FL USA ; Scottish Ctr Telehealth & Telecare, NHS 24, European Innovat Partnership Act & Hlth Ageing, Reference Site,EIP AHA, Glasgow, Lanark, Scotland ; Univ London Imperial Coll Sci Technol & Med, Dept Pediat, London, England ; Karolinska Inst, Inst Environm Med, Ctr Allergy Res, Stockholm, Sweden ; Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany ; Helmholtz Ctr Munich, ZAUM Ctr Allergy & Environm, Munich, Germany ; AQuAS, Barcelona, Spain ; European Reg & Local Hlth Assoc, EUREGHA, Brussels, Belgium ; Luliu Hatieganu Univ Med & Pharm, Allergol & Immunol Discipline, Cluj Napoca, Romania ; McMaster Univ, Dept Med, Div Clin Immunol & Allergy, Hamilton, ON, Canada ; Peercode DV, Amsterdam, Netherlands ; Rangueil Larrey Hosp, Dept Resp Dis, Toulouse, France ; Univ Paris 05, Hop Cochin, AP HP, Serv Physiol Resp, Paris, France ; Ss Cyril & Methodius Univ, Fac Med, Univ Clin Pulmol & Allergy, Skopje, Macedonia ; Ctr Hosp Univ Beni Messous, Serv Pneumoallergol, Algiers, Algeria ; Ecole Mines, Ales, France ; Vilnius Univ, Fac Med, Vilnius, Lithuania ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Allergy & Clin Immunol Sect, London, England ; Kings Coll London, Guys & St Thomas NHS Trust, London, England ; St Louis Univ, Sch Med, Sect Allergy & Immunol, St Louis, MO USA ; Umea Univ, Dept Comp Sci, Umea, Sweden ; Four Comp Oy, Halikko, Finland ; Ain Shams Univ, Pediat Allergy & Immunol Unit, Cairo, Egypt ; Social Serv & Publ Safety, Dept Hlth, Belfast, Antrim, North Ireland ; Global Allergy & Asthma Platform, Altgasse 8-10, A-1130 Vienna, Austria ; Bambino Gesu Childrens Res Hosp Holy See, Dept Pediat Med, Div Allergy, Rome, Italy ; Educ Hlth, Warwick, England ; Reg Hlth Serv Lazio Reg, Dept Epidemiol, Rome, Italy ; Athens Chest Hosp, Athens, Greece ; Natl Ctr Dis Control & Publ Hlth Georgia, Tbilisi, Rep of Georgia ; Istanbul Univ, Cerrahpasa Fac Med, Dept Pulm Dis, Istanbul, Turkey ; Clin Ricardo Palma, Allergy & Immunol Div, Lima, Peru ; Erasmus MC, Dept Internal Med, Sect Allergol, Rotterdam, Netherlands ; Univ Autonoma Nuevo Leon, San Nicolas De Los Garza, Mexico ; Latvian Assoc Allergists, Ctr TB & Lung Dis, Riga, Latvia ; Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA ; Univ Hosp Olomouc, Natl eHlth Ctr, Olomouc, Czech Republic ; Univ Chile, Clin Hosp, Immunol & Allergy Div, Santiago, Chile ; Odense Univ Hosp, Dept Resp Dis, Odense, Denmark ; German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany ; Vienna Challenge Chamber, Vienna, Austria ; Univ Coll Cork, Dept Paediat & Child Hlth, Cork, Ireland ; Univ Paris 11, Le Kremlin Bicetre, France ; Hop Bicetre, Serv Pneumol, Le Kremlin Bicetre, France ; INSERM, UMR S999, Le Kremlin Bicetre, France ; Univ Plymouth, Sch Psychol, Plymouth, Devon, England ; Univ Salerno, Dept Med & Surg, Baronissi, Italy ; Libra Fdn, Buenos Aires, DF, Argentina ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, London, England ; MRC & Asthma UK Ctr Allerg Mech Asthma, London, England ; Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium ; Montpellier Univ Hosp, Med Commiss, Montpellier, France ; Hallym Univ, Coll Med, Hallym Univ Sacred Heart Hosp, Anyang, Gyeonggi Do, South Korea ; Wroclaw Med Univ, Dept Clin Immunol, Wroclaw, Poland ; Ukrainian Med Stomatol Acad, Poltava, Ukraine ; Fed Medicobiol Agcy, Inst Immunol, Natl Res Ctr, Lab Mol Immunol, Moscow, Russia ; Hacettepe Univ, Sch Med, Pediat Allergy & Asthma Unit, Ankara, Turkey ; Hacettepe Univ, Sch Med, Dept Chest Dis, Immunol & Allergy Div, Ankara, Turkey ; Med Univ Lodz, Dept Family Med 1, Lodz, Poland ; McMaster Univ, Dept Med, Hlth Sci Ctr 3V47, 1280 Main St W, Hamilton, ON, Canada ; Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Dis, Groningen, Netherlands ; GARD, Geneva, Switzerland ; Univ Hosp Olomouc, Fac Med & Dent, Dept Resp Med, Olomouc, Czech Republic ; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Beatrix Childrens Hosp,Dept Pediat Pulmonol & Ped, Groningen, Netherlands ; Med Univ Lodz, Deptment Immunol Rheumatol & Allergy & HARC, Lodz, Poland ; Univ Helsinki, Childrens Hosp, Helsinki, Finland ; Vilnius Univ, Clin Infect Chest Dis Dermatol & Allergol, Vilnius, Lithuania ; Univ Ghent, VIB Inflammat Res Ctr, Ghent, Belgium ; Charite, Dept Pediat Pneumol & Immunol, Berlin, Germany ; Univ Med & Pharm, Hochiminh City, Vietnam ; Univ Tennessee, Coll Med, Dept Internal Med & Pediat, Div Allergy & Immunol, Germantown, TN USA ; Univ Dundee, Ninewells Hosp, Med Res Inst, Scottish Ctr Resp Res Cardiovasc & Diabet Med, Dundee, Scotland ; Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China ; Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway ; CHU Sart Tilman, Dept Pulm Med, Liege, Belgium ; Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Div Immunopathol, Vienna, Austria ; Univ Edinburgh, Queens Med Res Inst, Edinburgh, Midlothian, Scotland ; Hop St Joseph, Serv Pneumoallergol, Paris, France ; Univ Nantes, UMR INSERM, Serv Pneumol, UMR1087, Nantes, France ; Univ Nantes, Inst Thorax, CNR 6291, Nantes, France ; Rashid Hosp, Dept Pulm Med, Dubai, U Arab Emirates ; Biomax Informat AG, Munich, Germany ; Univ Bratislava, Dept Resp Med, Bratislava, Slovakia ; Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci, Coimbra, Portugal ; Ageing@Coimbra EIP AHA Reference Site, Coimbra, Portugal ; Bon Secours Hosp, Dept Med, Dublin, Ireland ; Kronikgune, Basque Region, Spain ; Univ Mississippi, Med Ctr, Div Clin Immunol & Allergy, Lab Behav Immunol Res, Jackson, MS USA ; Iranian Anti Tobacco Assoc, Tobacco Control Res Ctr, Tehran, Iran ; Maputo Cent Hosp, Dept Paediat, Maputo, Mozambique ; Allergy & Asthma Med Grp & Res Ctr, San Diego, CA USA ; Univ Montpellier, Dept Physiol, CHRU, PhyMedExp,INSERM U1046,CNRS UMR 9214, Montpellier, France ; Rhein Westfal TH Aachen, Univ Klinikum, Hautklin Klin Dermatol & Allergol, Aachen, Germany ; Croatian Pulm Soc, Zagreb, Croatia ; Natl Inst Pneumol M Nasta, Bucharest, Romania ; Univ Belgrade, Fac Med, Belgrade, Serbia ; Serbian Assoc Asthma & COPD, Belgrade, Serbia ; Caisse Assurance Retraite & Sante Travail Langued, Montpellier, France ; Tishreen Univ, Sch Med, Natl Ctr Res Chron Resp Dis, Latakia, Syria ; Paris Descartes Univ, Sorbonne Paris Cite, Dept Publ Hlth & Hlth Prod, EA 4064, Paris, France ; Paris Municipal Dept Social Act Childhood & Hlth, Paris, France ; Univ Cologne, Fac Med, Inst Med Stat Informat & Epidemiol, Cologne, Germany ; Padua Gen Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr Veneto Reg, Padua, Italy ; Russian Acad Med Sci, Sci Ctr Childrens Hlth, Moscow, Russia ; Hosp Ninos Orlando Alassia, Santa Fe, Argentina ; Hosp Hosp Bros Buda, Budapest, Hungary ; Hosp La Fe, Neumol & Alergol Infantil, Valencia, Spain ; Ctr Hosp Sao Joao, Dept Internal Med, Oporto, Portugal ; Univ Hosp Kinshasa, ENT Dept, Kinshasa, DEM REP CONGO ; Tokyo Natl Hosp, Natl Hosp Org, Tokyo, Japan ; Chiba Univ Hosp, Dept Otorhinolaryngol, Chiba, Japan ; Nippon Med Sch, Dept Otolaryngol, Tokyo, Japan ; Ctr Hosp Univ Pediatr Charles Gaulle, Ouagadougou, Burkina Faso ; Univ Hosp Pisa, Cardiothorac & Vasc Dept, Pisa, Italy ; Med Univ, Univ Vet Med, Messerli Res Inst, Dept Comparat Med, Vienna, Austria ; Charles Univ Prague, Fac Med, Dept Immunol & Allergol, Plzen, Czech Republic ; Charles Univ Prague, Fac Hosp Pilsen, Plzen, Czech Republic ; Univ Ferrara, Dept Med Sci, Resp Med, Ferrara, Italy ; Ajou Univ, Sch Med, Dept Allergy & Clin Immunol, Suwon, South Korea ; Univ Southern Denmark, Kolding, Denmark ; CUF Porto Hosp & Inst, Allergy Unit, Oporto, Portugal ; Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Otorhinolaryngol Head & Neck Surg, Mannheim, Germany ; Minist Econ Ind & Numer, Conseil Gen Econ, Paris, France ; Espace Francophone Pneumol, Soc Pneumol Langue Francaise, Paris, France ; CHU Grenoble, Dept Pediat, Grenoble, France ; Childrens Hosp Srebrnjak, Zagreb, Croatia ; Univ JJ Strossmayer, Sch Med, Osijek, Croatia ; Hietzing Hosp, Karl Landsteiner Inst Clin & Expt Pneumol, Vienna, Austria ; Med Univ Sofia, Clin Allergy & Asthma, Sofia, Bulgaria ; Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands ; Copenhagen Univ Hosp Gentofte, Allergy Clin, Lab Med Allergol, Copenhagen, Denmark ; Univ Aberdeen, Acad Ctr Primary Care, Aberdeen, Scotland ; Res Real Life, Cambridge, England ; German Ctr Lung Res DZL, Airway Res Ctr North, LungenClin Grosshansdorf, Grosshansdorf, Germany ; Univ Kiel, German Ctr Lung Res DZL, Airway Res Ctr North, Dept Med, Kiel, Germany ; Southampton Univ Hosp, NHS Fdn Trust, Southampton, Hants, England ; Coimbra Univ Hosp, Ctr Pneumol, Coimbra, Portugal ; Univ Valencia, Polibienestar Res Inst, Valencia, Spain ; Getafe Univ Hosp, Dept Geriatr, Madrid, Spain ; Assoc Asthme & Allergie, Paris, France ; Inst Invest Sanitaria Palma IdisPa, Primary Care Resp Res Unit, Palma De Mallorca, Spain ; Complesso Integrato Columbus, Allergy Unit, Rome, Italy ; Hosp Luz, Serv Imunoalergol, Lisbon, Portugal ; Univ Parana, Hosp Clin, Curitiba, Parana, Brazil ; Emek Med Ctr, Div Allergy Asthma & Clin Immunol, Afula, Israel ; Ctr Med Docente Trinidad & Clin El Avila, Allergy & Clin Immunol Dept, Caracas, Venezuela ; Autononous Univ Madrid, Fac Med, Madrid, Spain ; UCL, Royal Natl TNE Hosp, London, England ; Univ Palermo, DIBIMIS, Palermo, Italy ; Univ Zurich Hosp, Dept Dermatol, Allergy Unit, Zurich, Switzerland ; CHU Rangueil Larrey, Otolaryngol & Head & Neck Surg, Toulouse, France ; Queens Univ, Child Hlth, Belfast, Antrim, North Ireland ; Royal Belfast Hosp Sick Children, Belfast, Antrim, North Ireland ; Univ Joseph Fourier, Team Environm Epidemiol Appl Reprod & Resp Hlth, Univ Grenoble Alpes, INSERM,IAB U 1209, Grenoble, France ; Soc Paraguaya Alergia Asma & Inmunol, Asuncion, Paraguay ; Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands ; Univ Fed Sao Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, Sao Paulo, Brazil ; Euro Asian Resp Soc, Kyrgyzstan Natl Ctr Cardiol & Internal Med, Bishkek, Kyrgyzstan ; Univ Sao Paulo, Fac Med, Hosp Clin, Div Pulm,Inst Heart InCor, Sao Paulo, Brazil ; Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands ; European Union Geriatr Med Soc EUGMS, Helsinki, Finland ; Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Epidemiol, Maastricht, Netherlands ; IDIBAPS, Hosp Clin, Pneumol & Allergy Dept, Clin & Expt Resp Immunoallergy, Barcelona, Spain ; PELyon, Lyon, France ; Univ Claude Bernard Lyon, Hlth Serv & Performance Res, HESPER 7425, Villeurbanne, France ; Univ Hosp, Stockholm, Sweden ; Catholic Univ Louvain, Univ UCL Namur, Ctr Hosp Univ UCL Namur, Dept Chest Med, Yvoir, Belgium ; Philippines Soc Allergy Asthma & Immunol, Manila, Philippines ; Res Hosp, Arcispedale S Maria Nuova IRCCS, Dept Cardiol Thorac & Vasc Med, Pulm Unit, Reggio Emilia, Italy ; Reg Agcy Hlth & Social Care, Reggio Emilia, Italy ; Finnish Lung Assoc FILHA, Helsinki, Finland ; CNR Inst Clin Physiol, Pulm Environm Epidemiol Unit, Pisa, Italy ; CNR, Inst Biomed & Mol Immunol A Monroy, Palermo, Italy ; Sotiria Hosp, Athens, Greece ; Univ Klinikum Dusseldorf, HNO Klin, Dept Otorhinolaryngol, Dusseldorf, Germany ; Asthma UK, Mansell St, London, England ; Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Otolaryngol, Singapore, Singapore ; Hannover Med Sch, Dept Dermatol & Allergy, Div Immunodermatol & Allergy Res, Hannover, Germany ; Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA ; IPCRG, Aberdeen, Scotland ; Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England ; Olmsted Med Ctr, Dept Res, Rochester, MN USA ; Univ Cyprus, Sch Med, Nicosia, Cyprus ; Allergy & Asthma Inst, Lahore, Pakistan ; Univ Southampton, Social Sci, Southampton, Hants, England ; Univ Cape Town, Red Cross Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa ; Univ Cape Town, MRC Unit Child & Adolescent Hlth, Cape Town, South Africa ; Univ Catolica Cordoba, Cordoba, Argentina ; Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China ; Beijing Inst Otolaryngol, Beijing, Peoples R China ; Univ Clin Resp & Allerg Dis, Golnik, Slovenia ; Northern Hlth Alliance, Newcastle Upon Tyne, Tyne & Wear, England ; CHRU Arnaud Villeneuve, 371 Ave Doyen Gaston Giraud, Montpellier 5, France ; Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil ; Web of Science

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. ; Funding Agencies|National Cancer Institute (USA) [UM1 CA164920, CA 27469]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI 2007-3839, 2009 4363, RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318, NKI1998-1854, NKI2004-3088, NKI2007-3756]; Breast Cancer Research Trust, UK; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); NIHR Comprehensive Biomedical Research Centre; Guys and St. Thomas NHS Foundation Trust; Kings College London, United Kingdom; Oxford Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Instituto de Salud Carlos III; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI11/00923, PI12/00070]; California Breast Cancer Act of 1993; California Breast Cancer Research Fund [97-10500]; National Institutes of Health [R01 CA77398, CA128978]; California Department of Public Health; Lon V Smith Foundation [LVS39420]; Baden Wurttemberg Ministry of Science, Research and Arts; Deutsche Krebshilfe [107 352]; Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance; Institute of the Ruhr University Bochum (IPA), Bochum; Department of Internal Medicine; Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; Helsinki University Central Hospital Research Fund; Academy of Finland [266528, 250083, 122715]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; Friends of Hannover Medical School; Rudolf Bartling Foundation; special Government Funding (EVO) of Kuopio University Hospital grants; Cancer Fund of North Savo; Finnish Cancer Organizations; University of Eastern Finland; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales, Victoria; Cancer Council of New South Wales, Tasmania; Cancer Council of New South Wales, South Australia; Cancer Foundation of Western Australia; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council Victoria; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; National Health and Medical Research Council of Australia (NHMRC) [400413, 400281, 199600]; California Breast Cancer Research Program [1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098]; California Department of Health; National Cancer Institutes Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program [N01CN25403]; Stichting tegen Kanker [232-2008, 196-2010]; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419]; Hamburg Cancer Society; Italian Association for Cancer Research (AIRC); Italian citizens [5/1000]; Fondazione IRCCS Istituto Nazionale Tumori; Quebec Breast Cancer Foundation; Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program [CRN-87521]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Malaysian Ministry of Science, Technology and Innovation (MOSTI); Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer Research Initiatives Foundation (CARIF); Biomedical Research Council, Singapore [BMRC08/1/35/19/550]; National medical Research Council, Singapore [NMRC/CG/SERI/2010]; NIH [CA128978, R01CA100374, CA116167, CA176785, R01CA64277, R01CA148667, R37CA70867]; Finnish Cancer Foundation; Academy of Finland (Center of Excellence) [251314]; University of Oulu; University of Oulu Support Foundation; special Governmental EVO funds; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA; Marit and Hans Rausings Initiative Against Breast Cancer; Agency for Science, Technology and Research of Singapore (AstarSTAR); US National Institute of Health (NIH); Susan G. 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Grohne Family Foundation; Hellenic Cooperative Oncology Group research grant [HR R_BG/04]; Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II; European Union (European Social Fund - ESF); Greek national funds through Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) - ARISTEIA; Institute of Cancer Research (ICR), London; American Cancer Society [CRTG-00-196-01-CCE]; California Cancer Research Program [00-01389 V-20170, N01-CN25403, 2II0200]; Canadian Institutes for Health Research [MOP-86727]; Cancer Council Queensland; Cancer Institute of New Jersey; Celma Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve Appeal; Helse Vest; Imperial Experimental Cancer Research Centre [C1312/A15589]; Norwegian Cancer Society; Norwegian Research Council; Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Ministry of Health Labour and Welfare of Japan; L and S Milken Foundation; Polish Ministry of Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Cancer Research Initiatives Foundation; Roswell Park Cancer Institute Alliance Foundation; US National Cancer Institute [K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966, R01-CA063678]; US National Cancer Institute (Intramural research funds); US Army Medical Research and Material Command [DAMD17-01-1-0729, DAMD17-98-1-8659, DAMD17-02-1-0666, DAMD17-02-10669, W81XWH-10-1-0280]; National Health and Medical Research Council of Australia [400281, 199600]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]; Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and Katherine B. Andersen Foundation; Lon V. Smith Foundation [LVS-39420]; Oak Foundation; OHSU Foundation; Mermaid I project; Rudolf-Bartling Foundation; UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; Imperial College London; University College Hospital Womens Health Theme; Royal Marsden Hospital; WorkSafeBC; National Cancer Institute [UM1 CA164920, RC4CA153828]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08]; RTICC [06/0020/1060]; Mutua Madrilena Foundation (FMMA); City of Hope Clinical Cancer Genetics Community Network (COH-CCGCRN) [SAF2010-20493]; Hereditary Cancer Research Registry; Office of the Director, National Institutes of Health; Cancer Research - UK [C1287/A10118, C12292/A11174]; NHMRC Program Grant; Greek national funds through Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; European Social Fund; NIHR grant; Royal Marsden NHS Foundation Trust; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue Nationale Contre le Cancer; Association Le cancer du sein, parlons-en! Award; Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program; French National Institute of Cancer (INCa); Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant) [P30-CA051008]; Fisher Center for Familial Cancer Research; Swing Fore the Cure; GOA grant (Ghent University) [BOF10/GOA/019]; Ghent University Hospital; ISCIII (Spain) [RD12/0036/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Hospital Research Fund; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hong Kong Hereditary Breast Cancer Family Registry; Dr Ellen Li Charitable Foundation; Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228]; Norwegian EEA Financial Mechanism [Hu0115/NA/2008-3/OP-9]; Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, PIE13/00022, 2009SGR290, 2014SGR364]; Icelandic Association Walking for Breast Cancer Research; Landspitali University Hospital Research Fund; Canadian Breast Cancer Research Alliance [019511]; Ministero della Salute; Istituto Oncologico Veneto grant; Liga Portuguesa Contra o Cancro; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201, CA125183, R01 CA142996, 1U01CA161032]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; MH CZ - DRO (MMCI) [00209805]; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; Charles University in Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Research Fund; Intramural Research Program of the US National Cancer Institute, NIH; Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), NY; Russian Federation for Basic Research [13-04-92613, 14-04-93959, 15-04-01744]; NRG Oncology Statistical and Data Center [CA 37517]; NRG Oncologys Cancer Prevention and Control Committee [CA 101165]; Ohio State University Comprehensive Cancer Center; ITT (Istituto Toscano Tumori); Isreal cancer association; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Womens Cancer Research Alliance; CRUK; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Susan G. Komen Foundation; European Communitys Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; Post-Cancer GWAS initiative (GAME-ON initiative) [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; [KULPFV/10/016-SymBioSysII]; [P30 CA68485]; [FISPI08/1120]; [PBZ_KBN_122/P05/2004]

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. ; We thank all the individuals who took part in these studies and all the researchers, clin- icians, technicians and administrative staff who have enabled this work to be carried out, in particular those involved in the COGS project: Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, the staff of the CNIO genotyping unit, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissie ` re and Frederic Robidoux and the staff of the McGill University and Ge ́ nome Que ́ bec Innovation Centre, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. BCAC (acknowledgements by study) (ABCFS) : Maggie Angelakos, Judi Maskiell, Gillian Dite. (ABCS) C Ellen van der Schoot, Sanquin Amsterdam. (ACP) The ACP study wishes to thank the participants in the Thai Breast Cancer study. Special Thanks also go to the Thai Ministry of Public Health (MOPH), doctors and nurses who helped with the data collection process. Finally, the study would like to thank Dr Prat Boonyawongviroj, the former Permanent Secretary of MOPH and Dr Pornthep Siriwanarungsan, the Department Director-Generalof Disease Control who have supported the study throughout. (BBCS) Eileen Williams, Elaine Ryder-Mills, Kara Sargus (BIGGS) Niall McInerney, Gabrielle Colleran, Andrew Rowan, Angela Jones. (BSUCH) Peter Bugert, Medical Faculty Mannheim (CGPS) Staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen (CNIO-BCS) Guillermo Pita, Charo Alonso, Daniel Herrero, Nuria A ́ lvarez, Pilar Zamora, Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO)(CTS). The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, Yani Lu, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, Eunjung Lee, and Fred Schumacher at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, and Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine. (ESTHER) Hartwig Ziegler, Sonja Wolf, Volker Hermann. (GC-HBOC) Heide Hellebrand, Stefanie Engert and GC-HBOC (Supported by Deutsche Krebshilfe). (GENICA) The GENICA Network: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tu ̈bingen, Germany [HB, Wing-Yee Lo, Christina Justenhoven], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [UH], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bru ̈ning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth] (HEBCS) Kirsimari Aaltonen, Karl von Smitten, Sofia Khan, Tuomas Heikkinen, Irja Erkkila ̈ . (HMBCS) Natalia Antonenkova, Peter Hillemanns, Hans Christiansen and Johann H. Karstens (KBCP) Eija Myo ̈ ha ̈ nen, Helena Kemila ̈ inen. (kConFab/AOCS) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. (LAABC) We thank all the study participants and the entire data collection team, especially Annie Fung and June Yashiki. (LMBC) Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel and Kathleen Corthouts. (MARIE) Petra Seibold, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. (MCCS) MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index. (MBCSG) Bernard Peissel and Daniela Zaffaroni and Giulietta Scuvera of the Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; Monica Barile and Irene Feroce of the Istituto Europeo di Oncologia (IEO), Milan, Italy; and the personnel of the Cogentech Cancer Genetic Test Laboratory. (MTLGEBCS) We would like to thank Martine Tranchant (CHU de Que ́ bec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill Uni- versity) for DNA extraction, sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. (MYBRCA) Phuah Sze Yee, Peter Kang, Kang In Nee, Kavitta Sivanandan, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee, Teh Yew Ching and Nur Aishah Mohd Taib for DNA Extraction and patient recruitment. (NBHS) We thank study partcipants and research staff for their contributions and commitment to this study. (OBCS) Meeri Otsukka, Kari Mono- nen(OFBCR) Teresa Selander, Nayana Weerasooriya(ORIGO) We thank E. Krol-War- merdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. The LUMC survival data were retrieved from the Leiden hospital- based cancer registry system (ONCDOC) with the help of Dr J. Molenaar. (PBCS) Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner(pKARMA) The Swedish Medical Research Counsel. (RBCS) Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. (SASBAC) The Swedish Medical Research Counsel. (SBCGS) We thank study partcipants and research staff for their contributions and commitment to this study. (SBCS) Sue Higham, Helen Cramp, Ian Brock, Malcolm W. R. Reed, Sabapathy Balasubramanian and Dan Connley. (SEARCH) The SEARCH and EPIC teams. (SGBCC) We thank the participants and research coordinator Kimberley Chua. (SKKDKFZS) We thank all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. (TNBCC) Robert Pilarski and Charles Shapiro were instrumental in the formation of the OSU Breast Cancer Tissue Bank. We thank the Human Genetics Sample Bank for processing of samples and providing OSU Columbus area control samples. (UKBGS) We thank Breakthrough Breast Cancer and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ ICR NIHR Biomedical Research Centre. OCAC (acknowledgements by study) : This study would not have been possible without the contributions of the following: J Dennis, P. Hall (COGS); D. C. Tessier, F. Bacot, D. Vincent, S. LaBoissie ` re and F. Robidoux and the staff of the genotyping unit, (Genome Quebec); D. C. Whiteman, P. M. Webb, A. C. Green, N. K. Hayward, P. G. Parsons, D. M. Purdie, B. M. Smithers, D. Gotley, A. Clouston, I. Brown, S. Moore. K. Harrap, T. Sadkowski, S. O'Brien, E. Minehan, D. Roffe, S. O'Keefe, S. Lipshut, G. Connor . Berry, F. Walker, T. Barnes, J. Thomas, L. Terry, M. Connard, L. Bowes, M-R. Malt, J. White, C. Mosse, N. Tait, C. Bambach, A. Biankan, R. Brancatisano, M. Coleman, M. Cox, S. Deane, G. L. Falk, J. Gallagher, M. Hollands, T. Hugh, D. Hunt, J. Jorgensen, C. Martin, M. Richardson, G. Smith, R. Smith, D. Storey, J. Avramovic, J. Croese, J. D'Arcy, S. Fairley, J. Hansen, J. Masson, L. Nathanson, B. O'Loughlin, L. Rutherford, R. Turner, M. Windsor, J. Bessell, P. Devitt, G. Jamieson, D. Watson, S. Blamey, A. Boussioutas, R. Cade, G. Crosthwaite, I. Faragher, J. Gribbin, G. Hebbard, G. Kiroff, B. Mann, R. Millar, P. O'Brien, R. Thomas, S. Wood, S. Archer, K. Faulkner, J. Hamdorf (ACS); R. Stuart-Harris, F. Kirsten, J. Rutovitz, P. Clingan, A.Glasgow, A. Proietto, S. Braye, G. Otton, J. Shannon, T. Bonaventura, J. Stewart, S. Begbie, M. Friedlander, D. Bell, S. Baron-Hay, G. Gard, D. Nevell, N. Pavlakis, S. Valmadre, B. Young, C Camaris, R. Crouch, L. Edwards, N. Hacker, D. Marsden, G. Robertson, P. Beale, J. Beith, J. Carter, C. Dalrymple, R. Houghton, P. Russell, L. Anderson, M. Links, J. Grygiel, J. Hill, A. Brand, K. Byth, R. Jaworski, P. Harnett, R. Sharma,.G Wain, D. Purdie, D. Whiteman, B. Ward, D. Papadimos, A. Crandon, M. Cummings, K. Horwood. A. Obermair, L. Perrin, D. Wyld, J. Nicklin, M. Davy, M. K. Oehler, C. Hall, T. Dodd, T. Healy, K. Pittman, D. Henderson, J. Miller, J. Pierdes, A. Achan, P. Blomfield, D. Challis, R. McIntosh, A. Parker, B. Brown, R. Rome, D. Allen, P. Grant, S. Hyde, R. Laurie, M. Robbie, D. Healy, T. Jobling, T. Manolitsas, J. McNealage, P Rogers, B. Susil, E. Sumithran, I. Simpson, I. Haviv, K. Phillips, D. Rischin, S. Fox, D. Johnson, S. Lade, P. Waring, M. Loughrey, N.O'Callaghan, B. Murray, L. Mileshkin, P. Allan; V. Billson, J. Pyman, D. Neesham, M. Quinn, A. Hamilton, C. Underhill, R. Bell, L. F Ng, R. Blum, V.Ganju, I. Hammond, C. Stewart, Y. Leung, M. Buck, N. Zeps (ACS); G. Peuteman, T. Van Brussel and D. Smeets (BEL); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schu ̈rmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJO); G.S. Keeney, S. Windebank, C. Hilker and J. Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WYL (NHS); L. Paddock, M. King, U. Chandran, A. Samoila, and Y. Bensman (NJO); L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia- Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (POL); ); C. Luccarini, P. Harrington the SEARCH team and ECRIC (SEA); the Scottish Gynaecological Clinical Trails group and SCOTROC1 investigators (SRO); W-H. Chow, Y-T. Gao (SWH); Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/ (TCGA); I. Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan and J. Ford (UKO); Carole Pye (UKR); a full list of the investigators who contributed to the generation of the WTCCC data is available from http://www.wtccc.org.uk/ (WTCCC). CIMBA (acknowledgements by study) : (BCFR-AU) Maggie Angelakos, Judi Maskiell, Gillian Dite, Helen Tsimiklis. (BCFR-NY) We wish to thank members and participants in the New York site of the Breast Cancer Family Registry for their contributions to the study. (BCFR-ON) We wish to thank members and participants in the Ontario Familial Breast Cancer Registry for their contributions to the study. (BFBOCC-LT) We acknowledge Vilius Rudaitis, Laimonas Gris ˇ kevic ˇ ius, Ramu ̄ nas Janavic ˇ ius (if not in the authorship). BFBOCC-LV acknowledge Drs Janis Eglitis, Anna Krilova and Aivars Stengrevics. (BMBSA) We wish to thank the families who contribute to the BMBSA study. (BRICOH) We wish to thank Yuan Chun Ding and Linda Steele for their work in participant enrolment and biospecimen and data management.(CNIO) We thank Alicia Barroso, Rosario Alonso and Guillermo Pita for their assistance. (CONSIT TEAM) Alessandra Viel and Riccardo Dolcetti of the CRO Aviano National Cancer Institute, Aviano (PN), Italy; Laura Ottini of the 'Sapienza' University, Rome, Italy; Liliana Varesco of the IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Laura Papi and Gabriele Capone of the University of Florence, Florence, Italy; Antonella Savarese and Aline Martayan of the Istituto Nazionale Tumori Regina Elena, Rome, Italy; Stefania Tommasi and Brunella Pilato of the Istituto Nazionale Tumori 'Giovanni Paolo II', Bari, Italy. (CORE) The CIMBA data management and analysis is funded through Cancer Research- UK grant C12292/A11174. ACA is a Senior Cancer Research - UK Research Fellow. (EMBRACE) RE is supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. (FCCC) We thank Ms. JoEllen Weaver and Dr Betsy Bove for their technical support. (GEMO) Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study: National Cancer Genetics Network ) UNICANCER Genetic Group * , France. We wish to thank all the GEMO collaborating groups for their contribution to this study. GEMO Collaborating Centres are: Coordinating Centres, Unite ́ Mixte de Ge ́ ne ́ tique Constitutionnelle des Cancers Fre ́ quents, Hospices Civils de Lyon - Centre Le ́ on Be ́ rard, and Equipe ) Ge ́ ne ́ tique du cancer du sein * , Centre de Recherche en Cance ́ rologie de Lyon: Olga Sinilnikova w , Sylvie Mazoyer, Francesca Damiola, Laure Barjhoux, Carole Verny-Pierre, Me ́ lanie Le ́ one, Nadia Boutry-Kryza, Alain Calender, Sophie Giraud; and Service de Ge ́ ne ́ tique Oncologique, Institut Curie, Paris: Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Etienne Rouleau, Lisa Golmard, Agne ` s Collet, Virginie Moncoutier, Ce ́ drick Lefol, Muriel Belotti, Antoine de Pauw, Camille Elan, Catherine Nogues, Emmanuelle Fourme, Anne-Marie Birot. Institut Gustave Roussy, Villejuif: Brigitte Bressac-de-Pail- lerets, Olivier Caron, Marine Guillaud-Bataille. Centre Jean Perrin, Clermont–Ferrand: Yves-Jean Bignon, Nancy Uhrhammer. Centre Le ́ on Be ́ rard, Lyon: Christine Lasset, Vale ́ rie Bonadona, Sandrine Handallou. Centre Franc ̧ ois Baclesse, Caen: Agne ` s Hardouin, Pascaline Berthet, Dominique Vaur, Laurent Castera. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Audrey Remenieras, Franc ̧ ois Eisinger. CHU Arnaud-de-Villeneuve, Montpellier: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille: Jean-Philippe Peyrat, Joe ̈ lle Fournier, Franc ̧ oise Re ́ villion, Philippe Vennin w , Claude Adenis. Centre Paul Strauss, Strasbourg: Danie ` le Muller, Jean-Pierre Fricker. Institut Bergonie ́ , Bordeaux: Emmanuelle Barouk-Simonet, Franc ̧ oise Bonnet, Virginie Bubien, Nicolas Sevenet, Michel Longy. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU Grenoble: Dominique Leroux, He ́ le ` ne Dreyfus, Christine Rebischung, Magalie Peysselon. CHU Dijon: Fanny Coron, Laurence Faivre. CHU St-Etienne: Fabienne Prieur, Marine Lebrun, Caroline Kientz. Ho ˆ tel Dieu Centre Hospitalier, Chambe ́ ry: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice: Marc Fre ́ nay. CHU Limoges: Laurence Ve ́ nat-Bouvet. CHU Nantes: Capucine Delnatte. CHU Bretonneau, Tours: Isabelle Mortemousque. Groupe Hospitalier Pitie ́ -Salpe ́ trie ` re, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les- Nancy: Johanna Sokolowska, Myriam Bronner. CHU Besanc ̧ on: Marie-Agne ` s Collonge- Rame, Alexandre Damette. Creighton University, Omaha, USA: Henry T. Lynch, Carrie L. Snyder. (G-FAST) We wish to thank the technical support of Ilse Coene en Brecht Crombez. (HCSC) We acknowledge Alicia Tosar for her technical assistance(HEBCS) HEBCS would like to thank Dr Kristiina Aittoma ̈ ki, Taru A. Muranen, Drs Carl Blomqvist and Kirsimari Aaltonen and RNs Irja Erkkila ̈ and Virpi Palola for their help with the HEBCS data and samples. (HEBON) The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centres: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, J.L. de Lange, R. Wijnands; Erasmus Medical Center, Rotterdam, NL: J.M. Colle ́ e, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B. van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M. Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, NL: E.B. Go ́ mez- Garcia, M.J. Blok; University Medical Center Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer Organization (IKNL): S. Siesling, J.Verloop; The Dutch Pathology Registry (PALGA): L.I.H. Overbeek. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scien- tific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014- 187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON thanks the registration teams of IKNL and PALGA for part of the data collection. (HRBCP) We wish to thank Hong Kong Sanatoriuma and Hospital for their continual support. (HUNBOCS) We wish to thank the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Tibor Vaszko, Aniko Bozsik, Timea Pocza, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clin- icians and patients for their contributions to this study.(HVH) We wish to thank the Oncogenetics Group (VHIO), and the High Risk and Cancer Prevention Unit of the University Hospital Vall d'Hebron.(ICO) We wish to thank the ICO Hereditary Cancer Program team led by Dr Gabriel Capella. (INHERIT) We would like to thank Dr Martine Dumont, Martine Tranchant for sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. J.S. and P.S. were part of the QC and Genotyping coordinating group of iCOGS (BCAC and CIMBA). (IPOBCS) We wish to thank Drs Ana Peixoto, Catarina Santos, Patrı ́ cia Rocha and Pedro Pinto for their skilful contribution to the study. (KCONFAB) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. (MODSQUAD) Modifier Study of Quantitative Effects on Disease (MODSQUAD): we acknowledge ModSQuaD members Csilla Szabo (National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA); Lenka Foretova and Eva Machackova (Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic); and Michal Zikan, Petr Pohlreich and Zdenek Kleibl (Oncogynecologic Center and Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic). (MSKCC) Anne Lincoln, Lauren Jacobs. (NICCC) We wish to thank the NICCC National Familial Cancer Consultation Service team led by Sara Dishon, the lab team led by Dr Flavio Lejbkowicz, and the research field operations team led by Dr Mila Pinchev. (NRG Oncology) We thank the investigators of the Australia New Zealand NRG Oncology group. (OCGN) We wish to thank members and participants in the Ontario Cancer Genetics Network for their contributions to the study. (OSU CCG) Leigha Senter, Kevin Sweet, Caroline Craven, and Michelle O'Conor were instrumental in accrual of study participants, ascertainment of medical records and database management. Samples were processed by the OSU Human Genetics Sample Bank. (SEABASS) We would like to thank Yip Cheng Har, Nur Aishah Mohd Taib, Phuah Sze Yee, Norhashimah Hassan and all the research nurses, research assistants and doctors involved in the MyBrCa Study for assistance in patient recruitment, data collection and sample preparation. In addition, we thank Philip Iau, Sng Jen-Hwei and Sharifah Nor Akmal for contributing samples from the Singapore Breast Cancer Study nd the HUKM-HKL Study respectively. The Malaysian Breast Cancer Genetic Study is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HIR/MOHE/06) and charitable funding from Cancer Research Initiatives Foundation. (SMC) SMC team wishes to acknowledge the assistance of the Meirav Comprehensice breast cancer center team at the Sheba Medical Center for assistance in this study. (SWE-BRCA) Swedish scientists participating as SWE-BRCA collaborators are: from Lund University and University Hospital: Åke Borg, Håkan Olsson, Helena Jernstro ̈ m, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna O ̈ fverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza, Johanna Rantala; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellstro ̈ m Pigg, Richard Rosenquist; from Linko ̈ ping University Hospital: Marie Stenmark-Askmalm, Sigrun Lied- gren(UCHICAGO) We wish to thank Cecilia Zvocec, Qun Niu, physicians, genetic counsellors, research nurses and staff of the Cancer Risk Clinic for their contributions to this resource, and the many families who contribute to our programme. (UCLA) We thank Joyce Seldon MSGC and Lorna Kwan, MPH for assembling the data for this study. (UCSF) We would like to thank Dr Robert Nussbaum and the following genetic coun- sellors for participant recruitment: Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad. And thanks to Ms. Salina Chan for her data management. (UKFOCR) We thank Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. (VFCTG) Geoffrey Lindeman, Marion Harris, Martin Delatycki of the Victorian Familial Cancer Trials Group. We thank Sarah Sawyer and Rebecca Driessen for assembling this data and Ella Thompson for performing all DNA amplification. Grant Support : The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175—HEALTH-F2-2009- 223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community ́ s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The CIMBA data management and analytical work is funded by Cancer Research UK (C12292/A11174, C12292/A20861). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n ° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute. Personal support: K.L. is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). This project was supported in part by a Program Project Development Grant from the Ovarian Cancer Research Fund (S.A.G and A.M). The in vitro aspects of this project were performed within the Norris Cancer Centre at USC, which is supported in part by award number P30CA014089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. D.F.E. is a Principal Research Fellow of Cancer Research UK. A.C.A. is a Cancer Research—UK Senior Cancer Research Fellow. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. (WCP) B.Y.K is funded by the American Cancer Society Early Detection Professorship (SIOP- 06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. L.E.K. is supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). S.P.K. is supported by a Gates Cambridge Scholarship. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. RB was a Cancer Institute NSW Clinical Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. A.K.G. was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. S.L.E. and J.D.F. are supported by Fellowships from the National Breast Cancer Foundation (NBCF) Australia and NHMRC project grant (1058415). Funding : BCAC: The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The ACP study is funded by the Breast Cancer Research Trust, UK. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN).ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre.The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev HospitalThe CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tema ́ tica de Investigacio ́ n Cooperativa en Ca ́ ncer and grants from the Asociacio ́ n Espan ̃ ola Contra el Ca ́ ncer and the Fondo de Investigacio ́ n Sanitario (PI11/00923 and PI12/00070). The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is cur- rently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Wu ̈rttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC was supported by Deutsche Krebshilfe (107 352). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP), which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII.The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. (MBCSG) is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000'). The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701.MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19/550), Singapore and the National medical Research Council, Singa- pore (NMRC/CG/SERI/2010). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital-based research activities. The Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The pKARMA study was supported by Ma ̈ rit and Hans Rausings Initiative Against Breast CancerThe RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was sup- ported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network U19 CA148065.The SBCS was supported by Yorkshire Cancer Research S295, S299, S305PA and Sheffield Experimental Cancer Medicine Centre.SEARCH is funded by a programme grant from Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.SGBCC is funded by the NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/ 1/21/19/425.SKKDKFZS is supported by the DKFZ. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation, the Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, the European Union (European Social Fund – ESF), and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - ARISTEIA. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. Funding : OCAC : Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389 V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L and S Milken Foun- dation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50- CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01- CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01- CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01- CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01- CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01- CA071966, R01-CA063678 and Intramural research funds); the US Army Medical Research and Material Command (DAMD17-98-1- 8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1- 0669, W81XWH-10-1-0280); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wu ̈rttemberg through Medical Faculty of the University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital 'Womens Health Theme' and the Royal Marsden Hospital; WorkSafeBC. Funding : CIMBA (BCFR—all) : This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. (BFBOCC-LT) BFBOCC is partly supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; (BIDMC) BIDMC is supported by the Breast Cancer Research Foundation. (BMBSA) BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. (BRICOH) SLN was partially supported by the Morris and Horowitz Familes Endowed Professorship. (CBCS) This work was supported by the NEYE Foundation. (CNIO) This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilen ̃ a Foundation (FMMA) and SAF2010-20493 (COH-CCGCRN) City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. (CONSIT TEAM) Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to Siranoush Manoukian. (CORE) The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A11174 and C1287/A10118.SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer Research -UK Senior Cancer Research Fellow. (DEMOKRITOS) This research has been co-financed by the European Union (European Social Fund – ESF) and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Frame- work (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA. Investing in knowledge society through the European Social Fund.(DKFZ) The DKFZ study was supported by the DKFZ. (EMBRACE) EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. (FCCC) The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. (GC-HBOC) The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). (GEMO) The study was supported by the Ligue Nationale Contre le Cancer; the Association 'Le cancer du sein, parlons-en!' Award; the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and the French National Institute of Cancer (INCa). (GEORGETOWN) CI received support from the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial Cancer Research, and Swing Fore the Cure. (G-FAST) Kim De Leeneer is supported by GOA grant BOF10/ GOA/019 (Ghent University) and spearhead financing of Ghent University Hospital. (HCSC) HCSC supported by a grant RD12/0036/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. (HEBCS) The HEBCS was financially supported by the Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. (HEBON) The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection. (HRBCP) HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong (HUNBOCS) Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, OTKA K-112228 and the Norwegian EEA Financial Mechanism Hu0115/NA/2008-3/OP-9. (ICO) Contract grant sponsor: Asociacio ́ n Espan ̃ ola Contra el Ca ́ ncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/ 00748, PI13/00285, PIE13/00022, 2009SGR290 and 2014SGR364. (IHCC) The IHCC was supported by Grant PBZ_KBN_122/P05/2004(ILUH) The ILUH group was supported by the Icelandic Association 'Walking for Breast Cancer Research' and by the Landspitali University Hospital Research Fund. (INHERIT) This work was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI- 701. (IOVHBOCS) IOVHBOCS is supported by Ministero della Salute and '5 1,000' Istituto Oncologico Veneto grant. (IPOBCS) This study was in part supported by Liga Portuguesa Contra o Cancro.(KCONFAB) kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; (KOHBRA) KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs,Republic of Korea (1020350). (MAYO) MAYO is supported by NIH grants CA116167, CA128978 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. (MCGILL) Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade (MODSQUAD) MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). (MSKCC) MSKCC is supported by grants from the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin Research Fund. (NAROD) 1R01 CA149429- 01. (NCI) The research of Drs MH Greene, JT Loud and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. (NICCC) NICCC is supported by Clalit Health Services in Israel. Some of it's activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. (NNPIO) This work has been supported by the Russian Federation for Basic Research (grants 13-04-92613, 14-04-93959 and 15-04-01744). (NRG Oncology) This study was supported by National Cancer Institute grants to the NRG Oncology Administrative Office and Tissue Bank (CA 27469), the NRG Oncology Statistical and Data Center (CA 37517), and NRG Oncology's Cancer Prevention and Control Committee (CA 101165). (OSU CCG) OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. (PBCS) This work was supported by the ITT (Istituto Toscano Tumori) grants 2011-2013. (SEABASS) Ministry of Science, Technol- ogy and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. (SMC) This project was partially funded through a grant by the Isreal cancer association and the funding for the Israeli Inherited breast cancer consortium (SWE-BRCA) SWE-BRCA collaborators are supported by the Swedish Cancer Society. (UCHICAGO) UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor.(UCLA) Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. (UCSF) UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. (UKFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. (UPENN) National Institutes of Health (NIH) (R01-CA102776 and R01- CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. (UPITT/MWH) Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program;Hackers for Hope Pittsburgh. (VFCTG) Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation unding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n ° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/ A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund and grants R01-CA122443 and P50-CA136393. ; Sí

COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT ; COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220* ; Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group. ; French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D'Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France. ; CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children's Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France. ; Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium. ; COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O'Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d'Immunologie Clinique, d'Inflammation et d'Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children's Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children's Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children's Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome "Tor Vergata," Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d'Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort. ; NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. ; Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection. ; We thank the generous donation from Fisher Center for Alzheimer's Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project "Risposta immune in pazienti con COVID-19 e co-morbidità"), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by "Integrative Biology of Emerging Infectious Diseases" (grant no. ANR-10-LABX-62-IBEID), the "Fondation pour la Recherche Medicale" (grant FRM - EQU202003010193), the "Agence Nationale de la Recherche" (ANR FLASH COVID project IDISCOVR cofounded by the "Fondation pour la Recherche Médicale"), University of Paris ("Plan de Soutien Covid-19": RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by "Agence Nationale de la Recherche" (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris "PLAN D'URGENCE COVID19". LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and "Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19"). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine ; Peer reviewed

This book contains the abstracts of the papers/posters presented at the Tanzania Health Summit 2020 (THS-2020) Organized by the Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender, and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); & Tindwa Medical and Health Services (TMHS) held on 25–26 November 2020. The Tanzania Health Summit is the annual largest healthcare platform in Tanzania that attracts more than 1000 participants, national and international experts, from policymakers, health researchers, public health professionals, health insurers, medical doctors, nurses, pharmacists, private health investors, supply chain experts, and the civil society. During the three-day summit, stakeholders and decision-makers from every field in healthcare work together to find solutions to the country's and regional health challenges and set the agenda for a healthier future. Summit Title: Tanzania Health SummitSummit Acronym: THS-2020Summit Date: 25–26 November 2020Summit Location: St. Gasper Hotel and Conference Centre in Dodoma, TanzaniaSummit Organizers: Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); & Tindwa Medical and Health Services (TMHS).

High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. ; his work was primarily supported by the Bill & Melinda Gates Foundation (grant OPP1132415). Additionally, O Adetokunboh acknowledges the support of the Department of Science and Innovation, and National Research Foundation of South Africa. M Ausloos, A Pana, and C Herteliu are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, Executive Agency for Higher Education, Research, Development and Innovation Funding (Romania; project number PN-III-P4-ID-PCCF-2016-0084). T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. M J Bockarie is supported by the European and Developing Countries Clinical Trials Partnership. F Carvalho and E Fernandes acknowledge support from Portuguese national funds (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior; UIDB/50006/2020, UIDB/04378/2020, and UIDP/04378/2020. K Deribe is supported by the Wellcome Trust (grant 201900/Z/16/Z) as part of his International Intermediate Fellowship. B-F Hwang was partially supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. M Jakovljevic acknowledges support of the Serbia Ministry of Education Science and Technological Development (grant OI 175 014). M N Khan acknowledges the support of Jatiya Kabi Kazi Nazrul Islam University, Bangladesh. Y J Kim was supported by the Research Management Centre, Xiamen University Malaysia, Malaysia, (XMUMRF/2020-C6/ITCM/0004). K Krishnan is supported by University Grants Commission Centre of Advanced Study, (CAS II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar would like to acknowledge National Institutes of Health and Fogarty International Cente (K43TW010716). I Landires is a member of the Sistema Nacional de Investigación, which is supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama. W Mendoza is a program analyst in population and development at the UN Population Fund Country Office in Peru, which does not necessarily endorse this study. M Phetole received institutional support from the Grants, Innovation and Product Development Unit, South African Medical Research Council. O Odukoya acknowledges support from the Fogarty International Center of the US National Institutes of Health (K43TW010704). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. O Oladimeji is grateful for the support from Walter Sisulu University, Eastern Cape, South Africa, the University of Botswana, Botswana, and the University of Technology of Durban, Durban, South Africa. J R Padubidri acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India. G C Patton is supported by an Australian Government National Health and Medical Research Council research fellowship. P Rathi acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal India. A I Ribeiro was supported by National Funds through Fundação para a Ciência e Tecnologia, under the programme of Stimulus of Scientific Employment–Individual Support (CEECIND/02386/2018). A M Samy acknowledges the support of the Egyptian Fulbright Mission Program. F Sha was supported by the Shenzhen Social Science Fund (SZ2020C015) and the Shenzhen Science and Technology Program (KQTD20190929172835662). A Sheikh is supported by Health Data Research UK. N Taveira acknowledges partial funding by Fundação para a Ciência e Tecnologia, Portugal, and Aga Khan Development Network—Portugal Collaborative Research Network in Portuguese-speaking countries in Africa (332821690), and by the European and Developing Countries Clinical Trials Partnership (RIA2016MC-1615). C S Wiysonge is supported by the South African Medical Research Council. Y Zhang was supported by the Science and Technology Research Project of Hubei Provincial Department of Education (Q20201104) and Open Fund Project of Hubei Province Key Laboratory of Occupational Hazard Identification and Control (OHIC2020Y01).Editorial note: the Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations

High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. ; his work was primarily supported by the Bill & Melinda Gates Foundation (grant OPP1132415). Additionally, O Adetokunboh acknowledges the support of the Department of Science and Innovation, and National Research Foundation of South Africa. M Ausloos, A Pana, and C Herteliu are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, Executive Agency for Higher Education, Research, Development and Innovation Funding (Romania; project number PN-III-P4-ID-PCCF-2016-0084). T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. M J Bockarie is supported by the European and Developing Countries Clinical Trials Partnership. F Carvalho and E Fernandes acknowledge support from Portuguese national funds (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior; UIDB/50006/2020, UIDB/04378/2020, and UIDP/04378/2020. K Deribe is supported by the Wellcome Trust (grant 201900/Z/16/Z) as part of his International Intermediate Fellowship. B-F Hwang was partially supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. M Jakovljevic acknowledges support of the Serbia Ministry of Education Science and Technological Development (grant OI 175 014). M N Khan acknowledges the support of Jatiya Kabi Kazi Nazrul Islam University, Bangladesh. Y J Kim was supported by the Research Management Centre, Xiamen University Malaysia, Malaysia, (XMUMRF/2020-C6/ITCM/0004). K Krishnan is supported by University Grants Commission Centre of Advanced Study, (CAS II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar would like to acknowledge National Institutes of Health and Fogarty International Cente (K43TW010716). I Landires is a member of the Sistema Nacional de Investigación, which is supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama. W Mendoza is a program analyst in population and development at the UN Population Fund Country Office in Peru, which does not necessarily endorse this study. M Phetole received institutional support from the Grants, Innovation and Product Development Unit, South African Medical Research Council. O Odukoya acknowledges support from the Fogarty International Center of the US National Institutes of Health (K43TW010704). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. O Oladimeji is grateful for the support from Walter Sisulu University, Eastern Cape, South Africa, the University of Botswana, Botswana, and the University of Technology of Durban, Durban, South Africa. J R Padubidri acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India. G C Patton is supported by an Australian Government National Health and Medical Research Council research fellowship. P Rathi acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal India. A I Ribeiro was supported by National Funds through Fundação para a Ciência e Tecnologia, under the programme of Stimulus of Scientific Employment–Individual Support (CEECIND/02386/2018). A M Samy acknowledges the support of the Egyptian Fulbright Mission Program. F Sha was supported by the Shenzhen Social Science Fund (SZ2020C015) and the Shenzhen Science and Technology Program (KQTD20190929172835662). A Sheikh is supported by Health Data Research UK. N Taveira acknowledges partial funding by Fundação para a Ciência e Tecnologia, Portugal, and Aga Khan Development Network—Portugal Collaborative Research Network in Portuguese-speaking countries in Africa (332821690), and by the European and Developing Countries Clinical Trials Partnership (RIA2016MC-1615). C S Wiysonge is supported by the South African Medical Research Council. Y Zhang was supported by the Science and Technology Research Project of Hubei Provincial Department of Education (Q20201104) and Open Fund Project of Hubei Province Key Laboratory of Occupational Hazard Identification and Control (OHIC2020Y01).Editorial note: the Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020.

Using the data sets taken at center-of-mass energies above 4 GeV by the BESIII detector at the BEPCII storage ring, we search for the reaction e(+)e(-) -> gamma(ISR) X(3872) -> gamma(ISR)pi(+)pi(-) J/psi via the Initial State Radiation technique. The production of a resonance with quantum numbers J(PC) = 1(++) such as the X(3872) via single photon e(+)e(-) annihilation is forbidden, but is allowed by a next-to-leading order box diagram. We do not observe a significant signal of X(3872), and therefore give an upper limit for the electronic width times the branching fraction Gamma B-X(3872)(ee)(X(3872) -> pi(+)pi(-) J/psi) < 0.13 eVat the 90% confidence level. This measurement improves upon existing limits by a factor of 46. Using the same final state, we also measure the electronic width of the psi(3686) to be Gamma(psi)(ee)(3686) ee = 2213 +/- 18(stat) +/- 99(sys) eV. ; Funding: The BESIII collaboration thanks the staff of BEPCII and the IHEP computing center for their strong support. This work is supported in part by the National Key Basic Research Program of China under Contract No. 2015CB856700; National Natural Science Foundation of China (NSFC) under Contract Nos. 11125525, 11235011, 11322544, 11335008, 11425524; the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; Joint Large-Scale Scientific Facility Funds of the NSFC and CAS under Contract Nos. 11179007, U1232201, U1332201; CAS under Contract Nos. KJCX2-YW-N29, KJCX2-YW-N45; 100 Talents Program of CAS; INPAC and Shanghai Key Laboratory for Particle Physics and Cosmology; German Research Foundation DFG under Contract No. CRC-1044; Seventh Framework Programme of the European Union under Marie Curie International Incoming Fellowship Grant Agreement No. 627240; Istituto Nazionale di Fisica Nucleare, Italy; Ministry of Development of Turkey under Contract No. DPT2006K-120470; Russian Foundation for Basic Research under Contract No. 14-07-91152; U.S. Department of Energy under Contract Nos. DE-FG02-04ER41291, DE-FG02-05ER41374, DE-FG02-94ER40823, DESC0010118; U.S. National Science Foundation; University of Groningen (RuG) and the Helmholtzzentrum fur Schwerionenforschung (GSI), Darmstadt; WCU Program of National Research Foundation of Korea under Contract No. R32-2008-000-10155-0.

Daniel Levine on Hidden Hands, Vocation and Sustainable Critique in International Relations











Daniel Levine is part of a new generation
of IR scholars that takes a more pluralist approach to addressing the hard and
important questions generated by international politics. While many of those
interviewed here display a fairly consistent commitment to a certain position
within what is often referred to as 'the debate' in IR, Levine straddles the boundaries
of a diverse range of positions and understandings. Time to ask for
elaboration.














Print version of this Talk (pdf)




What is, according
to you, the biggest challenge / principal debate in current IR? What is your
position or answer to this challenge / in this debate?






The
question I'd like us to be asking more clearly than we are is, 'are we a
vocation and, if so, what kind of vocation are we'? This points to a varied set
of questions that we, as scholars, gesture to but spend relatively little
theoretical time developing or unpacking. There's an assumption that the
knowledge we produce is supposed to be put good for something, practical in
light of some praiseworthy purpose. Even theorists who perceive themselves to
be epistemologically value-free hope, I think, at least on an intuitive level, that
some practical good will emerge from what they do. They hope that they are doing
'good work' in the sense that some Christians use this term. But, there is not
really a sustained project of thinking through how those works work: how our notions of vocation might
be different or even mutually exclusive, and how the differences in our notions
of vocation might be bound up in non-obvious ways to our epistemological,
methodological, and theoretical choices.







Moreover,
except for a few very important and quite heroic (and minoritarian) efforts, we
don't really have a way to think systematically about the structure of the
profession: how it influences or intervenes or otherwise acts on particular
ideas as they percolate through it, and how those ideas get 'taken up' into
policy. Brian Schmidt has
done work like that, so has Inanna Hamati-Ataya,
Ole Waever, Ido Oren,
Oded Löwenheim, Elizabeth Dauphinee, Naeem Inayatullah,
and Piki Ish-Shalom; and it's good work, but
they are doing what they are doing with limited resources, and I think without due
appreciation from a big chunk of the field as to why that work is important and
what it means.







When
I started writing Recovering
International Relations, I had wanted to recover the 'view from nowhere'
that many social scientists idealize. You know, that methodological conceit
where we imagine we are standing on Mars, watching the earth through a
telescope, or we're Archimedes standing outside of the world, leveraging it
with distance and dispassion. I had worked on the Israeli-Palestinian conflict
for a long time, was living in Tel Aviv, working for a think tank, and was—am—an
Israeli citizen and an American citizen. I had this somewhat shocking discovery
right after the Second Intifada broke
out. Most of my senior colleagues were deploying their expertise in what seemed
to me to be a very tendentious way: to show why the second Intifada was Yassar
Arafat's fault or the Palestinian Authority's fault—or, in a few cases, the
Israelis' fault. There were some very simplistic political agendas that were
driving this research. People were watching the evening news, coming into work
the next morning, and then running Ehud Yaari's commentary through their respective fact-values-methods mill. Or if they were
well-connected, they were talking to their friends on the 'inside', and doing
the same thing.







It
was hard to admit this for a long time, but I was very naïve. I found that very
unsettling and quite disillusioning. That's why the view from nowhere was so
appealing. I wanted to be able to talk about
Israel and Palestine without taking a position on Israel and Palestine—but without eschewing the expertise I had
acquired along the way, in part because I was
a party to this conflict, and cared about its outcome. I was young,
inexperienced, and slightly arrogant to boot—neither yet a scholar, nor an 'expert,'
nor really aware of the game I was playing. So my objections were not well
received, nor did I pose them especially coherently. To their credit, my senior
colleagues did recognize something worthwhile in my diatribes, and they did
their best to help me get into graduate school.







As the
project developed, and as I started engaging with my mentors in grad school, it
appeared that the view from nowhere was essentially impossible to recover. With
Hegel and with the poststructuralists, we can't really think from nowhere; the
idea of it is this kind of intellectual optical illusion, as though thinking
simply happens, without a mind that is conditioned by being in the world. Therefore,
there needs to be a process by which we give account of ourselves.







There
are a variety of different ways to consider how one might do that. There's what
we might call the agentic approach, in which we think through the structure of
thought itself: its limitations, our dependence on a certain image of thinking
notwithstanding those limits—thought's work on us, on our minds. This is closest
to what I do, drawing on Adorno and Kant, and Adorno's account of how concepts
work in the mind; how they pull us away from the things we mean to understand
even as they give us the words to understand them. And drawing on Jane Bennett, William Connolly,
Hannah Arendt, Cornel West, JoanTronto, and JudithButler to think through how one
conditions oneself to accept those limitations from a space of love, humility
and service. Patrick Jackson's (TheoryTalk #44) Conduct of Research in IR is quite
similar to this approach; and so is Colin Wight's Agents, Structures and International
Relations; though they use more philosophy of science than I do.







One
could also do this more 'structurally.' One could say 'this is how the academy
works and this is how the academy interconnects with the larger political
community' and then try to trace out those links: I mentioned Hamati-Ataya,
Oren, and Ish-Shalom, or you could think of Isaac Kamola,
Helen Kinsella, or
Srdjan Vucetic.








Any of
those approaches—or really, some admixture of them—would be pieces of that
project. I would like us to be doing more of that—alongside, not instead of,
all the other things we are already doing, from historical institutionalism to formal
modeling, to large-N and quantitative approaches, and normative, feminist and
critical ones. I would like such self-accounting to be one of the things
scholars do, that they take it as seriously as they take methods, epistemology,
data, etc. Driving that claim home in our field, as it's presently constituted,
is our biggest challenge.






How did you arrive at where you currently are in IR?






I'm 42,
so the Cold War was a big deal. I'm American-born, and I was raised in a pretty
typical suburb. John Stewart from the Daily
Show is probably the most famous product of my hometown, though I didn't
know him. My view of history was a liberal and progressive in the Michael
Waltzer/Ulrich Beck/Anthony Giddens, vein, but I was definitely influenced by
the global circumstances of the time, and by the 'End of History' discourse
that was in the air. I thought that the US was a force of good in the world. I
was a nice Jewish boy from New Jersey. I really wanted to live in Israel for
personal reasons, and the moral challenge of living in Israel after the
Intifada seemed to go away with the peace process. So, it seemed to me that it
was a kind of golden moment: you could 'render unto Caesar what was due to Caesar',
and do the same for the Lord. I could actually be a Jewish-Israeli national and
also a political progressive. (That phrase is, of course, drawn from the Gospels,
and that may give you some sense of how my stated religious affiliations might
have differed from the conceptual and theological structures upon which they actually
rested—score one for the necessity of reflexivity. But in any case, those
events were important.)







I moved
to Israel when I was 22 and was drafted into the military after I took
citizenship there. In the IDF, I was a low-level functionary/general laborer—a
'jobnik', someone who probably produces less in utility than they consume in
rations. Our job was to provide support for the combatants that patrolled a
certain chunk of the West Bank near Nablus—Shechem, as we called it, after the
biblical name. I was not a particularly distinguished soldier. But we were cogs
in a very large military occupation, and being inside a machine like that, you
can see how the gears and pieces of it meshed together, and I started taking
notice of this. Sometimes I'd help keep the diary in the operations room. You
saw how it all worked, or didn't work; or rather, for whom it worked and for
whom it didn't. All that was very sobering and quite fascinating.







I once
attended a lecture given by the African politics scholar Scott Straus, and he
said the thing about being present right after genocide is that you come across
these pits full of dead bodies. It's really shocking and horrific—there they
are, just as plain as day. Nothing I saw in the sheer level of violence compares
to that in any way—I should stress this. But that sense of it all just being out there, as plain as day, and being
shocked by this—that resonated with me. Everyone who cared to look could
understand how the occupation worked, or at least how chunks of it worked. So I
would say in terms of events, those things were the big pieces that structured
my thinking.







Here's two
anecdotal examples. Since I was a grade of soldier with very limited skills, I
was on guard duty a lot. We had a radio. I could hear the Prime Minister on the
radio saying we are going to strike so-and-so in response to an attack on such-and-such,
and then I could see helicopters pass overhead to Nablus, and then I could see
smoke. Then I could see soldiers come back from going out to do whatever it was
the helicopter had provided air support for. I'd see ambulances with red
crescents or red Stars of David rush down the main road. It began to occur to
me that there was a certain economy of violence in speech and performance. I
didn't think about it in specifically theoretical terms before I went back to
graduate school, but Israelis had been killed, political outrage had been
generated. There was a kind of affective deficit in Israeli politics that
demanded a response, and some amount of suffering had to be returned—so the
government could say it was doing its job. I found this very depressing. My odd
way of experiencing this—neither fully inside nor outside—is certainly not the
most important or authentic, and I'm not trying to set myself up as an expert
on this basis. I'm only trying to account for how it made me think at the time
and how that shows up in what and how I write now.







Later,
when I was in the reserves, I was in the same unit with the same guys every
year. One year, we were lacing our boots and getting our equipment for our
three weeks of duty in a sector of the West Bank near Hebron, I think it was. I
remember one guy, one of the more hawkish guys, said 'we'll show 'em this time,
we'll show them what's what'. Three weeks later, that same guy said 'Jeez, it's
like we're like a thorn in their backside; no wonder they hate us so much.' (He
actually used some colorful imagery that I can't share with you.) I remember
thinking, 'well, ok, he'll go home and he'll tell his family and his friends;
some good will come of this.' The next year, I saw the same guy saying the same
thing at the start, 'we'll show those SOBs.' And then three weeks later, 'oh my
God, this is so pointless, no wonder they hate us…' So after a few years of
this I finally said to him, 'tagid, ma
yihiyeh itcha?'—Like, dude, what's your deal? 'We've had this conversation every year! What happens to you in
the 48 weeks that you're not here that you forget this?' And I think he looked
at me like, 'what are you talking about?'







I
thought about that afterwards: we have these moments of experience when we're
out of our everyday environment and discourse, the diet of news and fear, PR
and political nonsense—that's when these insights become possible. So, when
this guy comes in and says 'ok, we'll get those SOBs,' he's carrying with him this
discourse that he has from home, from the news and TV, from his 'parliament'
with his friends where they get together and talk about politics and war and
economics and whatever else—and then a few weeks of occupation duty disrupts
all that, makes him see it in a different light, and he has these kinds of
fugitive experiences which give him a weirdly acute critical insight. Suddenly,
he's this mini-Foucault.







In a
few weeks, though, he goes back to his life, there's no space or niche into
which that uncomfortable, fugitive insight can really grow, so it just sort of
disappears or withers on the vine, its power is dissipated. This is a very
real, direct experience of violence and it's covered over by all of this
jibber-jabber. So there's a moment where you start to wonder: what exactly
happens there? What happens in those 48 weeks? What happens to me during those weeks? You can see how a
kind of ongoing critical self-interrogation would evolve out of that. Again,
none of those things are exactly what my book's about, but it gives you a sense
of how you might find Adorno's kind of critical relentlessness and negativity vital
and important and really useful and necessary. You can see how that might
inform my thinking.







In
terms of books, as an undergraduate, I had read, not very attentively, Said and
Foucault, and all of the stuff at the University of Chicago we had to take in
what they called the 'Scosh Sequence,' from sociologists like Elijah Anderson
and William Julius Wilson to Charles Lindblom and Mancur Olsen: texts from the
positive and the interpretive to the post-structural. I had courses with some
very smart Israeli and Palestinian profs—Ephraim Yaar, Salim Tamari, Ariela
Finkelstein. And of course Rashid Khalidi was there at that time. Once I was in
the military, the Foucault and Said suddenly started popping around in my head.
Suddenly, this sort of lived experience of being on guard duty made the
Panopticon and the notion of discipline go from being a rather complicated,
obscure concept to something concrete. 'Oh! That's
what discipline is!'







When I
went back to graduate school, I was given a pretty steady diet of Waltz,
rational deterrence theory, Barry Posen, Stephen Walt (Theory Talk #33), and Robert Jervis (Theory Talk #12). Shai
Feldman was a remarkable teacher, so were Ilai Alon in philosophy, Shlomo
Shoham in sociology and Aharon Shai in History. Additionally I had colleagues
at work who were PhD students at the Hebrew University working with Emanuel Adler;
they gave me Wendt (Theory Talk #3), Katzenstein's (TheoryTalk # 15) Culture of National Security, Adler and
Barnett, and Jutta Weldes' early article on 'Constructing National Interests'
in the EJIR (PDF here).
My job was to help them publish their monographs, so I got really into the guts
of their arguments, which were fascinating. I am not really an agency-centered
theory guy anymore and I am not really a constructivist anymore, but that stuff
was fantastic. I saw that one could write from a wholly different viewpoint,
perspective, and voice. This is all very mainstream in IR now, but at the time,
it felt quite edgy, very novel. Part of the reason why the middle chapters of Recovering IR has these long discussions
about different kinds of constructivism is that I wouldn't have had two
thoughts to rub together if it was not for those books. I do disagree with them
now and strongly, but they were very important to me all the same.






What would a student need to become a specialist in IR or understand the
world in a global way?






I'd be
more comfortable answering that question as someone who was, until relatively
recently, a grad student. I've not been productive long enough to say 'Well,
here's how to succeed in this business and be a theorist of enduring substance
or importance' with any authority. But I can say, 'here's how I'm trying to be
one.' There's a famous article by Albert O. Hirschman called 'The Principle of
the Hiding Hand,' (PDF here)
and in it he says that frequently, the only way one can get through really
large or complicated projects is to delude oneself as to how hard the project
is actually going to be. He takes as an example these ambitious, massively
complicated post-colonial economic projects of the Aswan High Dam variety. The
only way such enormous projects ever get off the ground, he says, is if one
either denies their true complexity or deludes oneself. Otherwise you despair
and you never get it done. From the first day of seminar to dissertation
proposal to job—thank God I had no idea what I was in for, or I might have
quit.







Also,
the job market being what it was, we had to be very, very passionate scholars who
wrote and argued for the sheer intellectual rush and love of writing. And yet,
we also had to be very practical and almost cynical about the way in which the
academic market builds on the prestige of publications and the way in which
prestige becomes shorthand for your commodity value. At least in the US, the
decline of tenure and the emergence of a kind of new class of academics whose
realm of responsibility is specifically to engage in uncomfortable kinds of
political and moral critique—but without tenure, and at the mercy of a sometimes
feckless dean, an overburdened department chair or fickle colleagues—that's very scary. If you're doing 'normal
science', it's a different game and the challenges are different. But if your
job is to do critique, in the last ten years, it's a very big deal. Very
difficult. I'm very fortunate in that regard; at Alabama I've had great support
from my department, my chair, and my college.







I was a
Johns Hopkins PhD, and my department was fantastic in terms of giving me
support, encouragement, getting out of my way while throwing interesting books
at me, reading drafts that were bad and helping me make them good—or at least
telling me why they were bad. We did
not get particularly good professional training, because I think they did not
want us to get professionalized before we found our own voice. I'm really
grateful for that, truly. But then there's this period in which you have to
figure out how to make your voice into a commodity. That's really tough, it's a
little bit disheartening—even to discover that you must be a commodity is dismaying; didn't we go into the academy to avoid
this sort of logic? But just like Marx says, commodities have a double life, and
so do you. The use-value of your scholarship and its exchange-value do not
interlock automatically and without friction. So you spend all this time on the
use-value of it—writing a cool, smart, interesting dissertation—thinking that
will translate into exchange-value, and it turns out that it sort of does, but
a lot of other things translate into exchange-value too that aren't really about
how good your work is necessarily. And many of your colleagues, if what you're
doing is original, won't really understand what you're doing; the value or the
creativity of it won't be apparent to them unless they spend a lot of time sifting
through your bad drafts of it, which only a few—but God bless those—will do. So
how you create exchange-value for yourself is important. So is finding people
who will care about you, your project, your future—and learning when to take
their advice, when to ignore it, and how to do so tactfully.







If all that's
hard, you're probably doing it right. It's unfortunate that that's how it is,
but at all events, that's how it was for me.











Would you elaborate on the concept of
vocation and why this is so important to the view from nowhere? It is important
to say that the view from nowhere is perhaps difficult. So is vocation, or a
kind of Weberian approach, a way to articulate that for you?







There's
a quote in a book from a Brazilian novelist named Machado de Assis. His
protagonist is this fellow Bras Cubas, who's writing a posthumous memoir of his
own life. He's writing from beyond the grave. From there, he can view his whole
life and his entire society from outside; he's finally achieved positivism's
view from nowhere. But the thing about this view—and the book means to be a
sendup of the Comtean positivism that was fashionable in Brazil in those
days—is that it gives him no comfort. He now knows why he lived his life the
way he did; how he failed and what was—and what was not—his fault. The
absurdity of it all makes sense. But it changes nothing: he has died
unfulfilled, unloved, and essentially alone: a minor poet and back-bench politician
who was ultimately of little use to anyone nor of much to himself. All he knows
is how that happened.







In the
end, if we're all playing a role in how a world comes into being and it's in
some sense our job simply to accept this, and our job as scholars merely to
explain it, this gives us no comfort in the face of suffering, in the face of
violence and evil. To some extent as scholars, and to some extent as a
discipline, we exist as a response to evil, to suffering, to foolishness, to
folly; it's not a coincidence that the first professorship of IR is created in
Britain in the wake of WWI, and that it's given to someone like E. H. Carr.







If we
don't have a view from nowhere because we've given up anything like a moral
sense that can't be reduced to fractional, material, or ideological
sensibilities, and if we know that sometimes those 'views from somewhere' can
provide cover for terrible kinds of evil or justify awful kinds of suffering,
then the notion of vocation seems to come in at that point and say well,
'here's what I hope I'm doing', or 'here's what I wish to be doing', or 'here's
what I'd like to think I'm doing', and then allowing others to weigh in and
give their two cents. Vocation, in the sense of Weber's lectures, comes out of
that. It's Kant for social scientists: What can I know? What should I do? For
what may I hope? In other words, what the necessity and obligation of thinking
is on the one hand, and on the other what its limitations are.







This is
a way to save International Relations from two things: one, from relativism and
perspectivism, and the other, from a descent into the technocratic or the
managerial. I am trying to stand between the two. My own intellectual
background was in security studies at Tel Aviv University in the 1990s: the
period immediately after Maastricht, in the period of the Oslo Process, the end
of Apartheid. My hope back in the days when the peace process seemed to me to
be going well was that I'd be able to have a kind of technocratic job in
Israel's Ministry of Foreign Affairs or Defense. Counting tanks, or something
similar. I thought that would be a pretty good job. I would be doing my part to
maintain a society that had constructed a stable, long-term deterrent by which
to meaningfully address the problem of Jewish statelessness and vulnerability,
but without the disenfranchisement of another people. I could sit down and
count my tanks with a clear conscience, because the specter of evil was being
removed from that work. The problem of the occupation was being be solved.
Again, it's somewhat embarrassing to admit this now.







I would
say in the US academy, there is definitely a balance in favor of the
technocrats. We have enormous machines for the production and consumption of
PhDs in this country. The defense establishment is an enormous player. Groups
like the Institute for Defense Analysis need a lot of PhDs, the NSF funds a lot
of PhDs (for now, at least), and that tips the balance of the profession in a
certain way. My ability to use ideas compellingly at ISA won't change that fact
all by itself, there's a base-superstructure issue in play there.







In
Europe, it's a different story, for a bunch of reasons. The defense
establishments of the EU member states aren't as onerous a presence. And, there
are more of them; so there's a kind of diversity there and a need to think
culturally about how these various institutions interlock and how people learn
to talk to each other: the Martha Finnemore-to-Vincent Pouliot-to-Iver Neumann (Theory Talk #52) study of ideas and institutions and
officials. Plus, you have universities like the EUI and the CEU, which are not
reducible to any particular national interest or education system; creating
knowledge, but for a political/state form that's still emergent. No one knows
exactly what it is, what its institutions and interests will ultimately be.
Because of that, it's hard to imagine the EUI producing scholars with obviously
nationally-inflected research programs, like Halford Mackinder,
Mahan, Ratzel from a century
ago. There will still be reifications and ideologies, but there's more 'give'
since the institutions are still in play. And there's fantastically interesting
stuff happening in Australia, and in Singapore—think of people like Janice
Bialley-Mattern, Tony Burke and Roland Bleiker.











Critique has a long and controversial
history in our discipline. Could you perhaps elaborate, as a kind of background
or setting, how critique can be used in IR and why you've placed it at the
center of your approach to IR theory?







Critique
as term of art comes into the profession through Robert Cox (Theory Talk #37) and through the folks that were writing
after him in the '90s, including Neufeld, Booth, Wyn-Jones, Rengger, Linklater and
Ashley—though pieces of the reflexive practice of critique are present in the
field well before. For Cox, the famous line is that theory is always 'for
something and for someone.' The question is, if that's true how far down does
that problem go? Is it a problem of epistemology and method, or is it a problem
of being as such, a problem of ontology? Is it fundamental to the nature of
politics?







If the
set of processes to which we refer when we speak of 'thinking' is inherently
for someone and for something, and that problem harkens back to the idea that
all thinking is grounded in one's interests and perspectives, i.e., that all
practical or systematic attempts to understand politics are 'virtuous' in the
Machiavellian sense (they serve princely interests) but not necessarily in the Christian
sense (deriving from transcendent values), then we have a real problem in keeping
those two things separate in our minds. Think of Linklater's book Men and Citizens in International Relations
as a key node in that argument, though Linklater ultimately believes (at least
in that book) that a reconciliation between the two is possible. I'm less
convinced.







Now
recall the vocation point we discussed before. IR as a discipline has a deep
sense of moral calling which goes beyond princely interest. And the traditions
on which it draws are as much transcendently normative as anything else. So
encoded in our ostensibly practical-Machiavellian analyses is going to be
something like a sense of Christian virtue; we'll believe we're not merely
correct in our analyses, but really and
truly right in some otherworldly, transcendent way. True or not, that sense
of conviction will attach itself to our thinking, to the political forces and
agendas that we're serving. We'll come to believe that we are citing
Machiavelli in the service of something greater: whether that's 'scientific
truth' or the national interest, or what have you. Nothing could be more
dangerous than that. Critique, as an intervention, comes here: to dispel or
chasten those beliefs. Harry Gould, Brent Steele, and especially Ned Lebow (Theory Talk #53) write about prudence and a sense of
finitude: these are the close cousins of this kind of critique.







If we
take seriously the notion that people sometimes fight and kill in the service
of really awful causes while believing they are doing right, and that scholars
sometimes help them sustain those convictions rather than disabuse them of them—even
if they do not intend this—then critique becomes an awfully big problem and it
really threatens to undermine the profession as such. It opens up a whole new
level of obligation and responsibility, and it magnifies what might otherwise
be staid 'inside baseball'—Intramural scholarly or methodological debates. Part
of the reason why the 'great debates' were so great—so hotly fought—had to do
with this: our scholarly debates were, in fact, ideological ones.







It
undermines the field in another way as well. If we take critique seriously,
there's got to be a lot of moral reflection by scholars. That will make it hard
to produce scholarship quickly, to be an all-purpose intellectual that can
quickly produce thought-product in a policy-appropriate way, because I will
want to be thinking from another space, and of course precisely what
policy-makers want is that you don't
think from some other space; that you present them with 'shovel ready' policy
that solves problems without creating new ones.







So you
now have not just a kind of theoretical or methodological interruption in the
discussion of, say, absolute or relative gains. You now have to give an account
of yourself. And for me, that's what critique in IR means. To unpack the
definition I gave above, it's the attempt to give an account of what the duties
and limits of one's thinking are in the context of politics, given the nature
of politics as we understand it. Because IR comes out of the Second World War,
we're bound to take the most capacious notions of what political evil and
contingency can be; if we are not always in the midst of genocide and ruin,
then we are at least potentially so. And so contingency and complexity and all
the stuff that we're talking about must face that. I want to hold out that Carl
Schmitt and Hans Morgenthau might be
right—in ways which neither they, nor I, can completely fathom. Then I have
to give accounts of thinking that take a level of responsibility commensurate
with that possibility.







In that
vein, when I look at accounts of thinking in the context of the political, when
I look at what concepts are and how they work and how they do work on the world
so that it can be rendered tractable to thought, I realize that what we come up
with when we're done doesn't look very much like politics anymore. We have
tools which, when applied to politics, change it quite dramatically; they reify
or denature it. To be critical in the face of that, you're going to be obliged
to an extensive degree of self-interrogation and self-checking, which I call chastening.







That process
of chastening reason, is, in effect, what remains of the enlightenment obligation
to use practical reason to improve what Bacon called the human estate. What's
left of that obligation is to think in terms of the betterment of other human beings
as best as you can, knowing you can't do that very well, but that you may still
be obliged to try.







That's
really hard to do and it's an odd form of silence and non-silence. After all,
if I were to look at the Shoah while it was happening, or look at what happened
in Rwanda, and say 'well, I don't really have a foundational position on which
to stand so I can't analyze or condemn that'—that would not be a morally
acceptable position. Price and Reus-Smit (TheoryTalk #27) say this
in their 1998 article and they are absolutely right. But then there's the fact
that I don't quite know what to say beyond 'stop murdering people!' The world
is so easy to break with words, and so hard to put back together with them—assuming
anyone cares at all about anything we say. So I am obliged to respond to those
kinds of events when I see them, and I am also obliged to acknowledge that I
can't respond to them well, because my authority comes from the conceptual tools
I have, and they aren't really very good. Essentially, what I'm doing as
scholar of IR is the equivalent is using the heel of my shoe to hammer in a nail.
(That's a nice line, no? I wish it was mine, but it's Hannah Arendt.) It will
probably work, but it will take a while, and the nail won't go in so straight. To
chasten one's thinking is to remind oneself that the heel of one's shoe is not
yet a hammer; that all we're doing is muddling through—even when we do our work
with absolute seriousness and strict attention to detail, context and method—as
of course we should.











You discuss IR theory in terms of different
reifications. In which was does that also lead you to take a stand against a Weberian
understanding of IR?







I think
where I depart from Weber is that he has more faith than I do that, at some
point, disenchantment produces something better. There is faith or hope on
their part that the iron cage that we experience as a result of disenchantment
and as a result of the transformation from earlier forms of charismatic and
traditional authority to contemporary rational ones won't always be oppressive,
not forever. New forms and ways of being will emerge, in which those
disenchanted modes actually will fulfill their promise for a kind of
improvement in the human estate. If it's a long, complicated process—hence the
image of slow boring into hard wood—but faith is still justified, good things
can still happen.







For me,
the question is how would you manage a society that is liable to go insane or
to descend into moments of madness because of the side-effects or intervening
effects of disenchantment and modernization, while holding fast to the notion
that at some point, this is going to get better for most people? I'm a bit less
certain about that than I read Patrick and Weber being. I think that even if
they're right, it makes sense morally as scholars, not necessarily as citizens
or individuals or people, to dwell in the loss of those who fall along the way.








I find
myself thinking about the people who are gone a lot. My ex-wife teaches on
slavery, and I think a lot about this terrible thing she once told me. On slave
ships, when there was not enough food they would throw the people overboard
because ship masters got insurance money if their property went overboard, but
not if human beings succumbed on-ship. There's a scene depicting this in
Spielberg's film Amistad and it
haunts me. I find myself thinking about those people, dragged under with their
chains. I wonder what they looked like, what they had to say. I wonder what
they might have created or how their great-great grandchildren children would
have played with my child. I wonder if my best friend or true love was never
born because her or his ancestor died in this way. An enormous number of people
perished. I can't quite believe this, even if I know it's true.







Yoram
Kaniuk, the recently deceased Israeli novelist, wrote that the Israeli state was
built on the ground-up bones of the Jews who couldn't get there because it was
founded too late. I wonder about them too. And when I taught course modules on
Cambodia, I would find myself looking at the photographs made of the people in
Tuol Sleng before they were killed, the photo archives which the prison kept
for itself. There is a mother, daughter, father, brother, son, and I find
myself drawn into their eyes and faces. I don't want those people to disappear
into zeros or statistics. I want somehow to give them some of their dignity
back, and I want to dwell in the tragic nature my own feeling because it bears
remembering that I cannot ever really do that. If I remember that, I will have
some sense of what life's worth is, and I won't speak crassly about
interventions or bombings or wars—wherever I might come down on them. I would
say that it's almost a religious obligation to attend to the memory of those
people. My desire to abide with them makes me very, very suspicious of hope or
progress. I want this practice of a kind of mourning or grief to chasten such
hope.







There's
a problem with that position. Some will point out to me that this will turn
into its own kind of Manichean counter-movement, a kind of Nietzschean ressentiment. Or else that dwelling in
mourning has a self-congratulatory quality to it. And there are certainly
problems with this position at the level of popular or mass politics. We do see
a lot of ressentiment in our
politics. On the left, there's a lot of angry, self-aggrandizing moral
superiority. And you can think about someone like Sarah Palin in the US as a
kind of populist rejection of guilt and responsibility from the right.







But as social
scientists, we might have space to be the voice for that kind of grief, to take
it on and disseminate the ethics that follow from it; to give that grief a
voice. That kind of relentless self-chastening is what I'm all about. I think
it opens you up to new agendas and possibilities. I think it's a much deeper
way to be 'policy relevant' than most of my colleagues understand this term. If
we are relentlessly self-critical as scholars, and if we relentlessly resist
the appropriation of scholarly narratives to simplistic moral or political ends
and if we, as a society, help to build an intolerance of that and a sense of
the mourning that comes out of that, we also open our society up to say things
like, 'ok, well what's left?'







And
then, well, maybe a lot of things are left, and some of them are not so bad. Maybe
we start to imagine something better. That's where I'd rejoin Jackson and
Weber; after that set of ethical/emotional/spiritual moves. I think, by the
way, that Patrick mostly agrees with me; it's only a question of what his work
emphasizes and what mine has emphasized. On this point, consider Ned Lebow's
notion of tragedy. He and I disagree on some of the details of that notion. But
on top of his remarkable erudition, he's a survivor of the Shoah. I suspect he has thought very deeply about grief and
mourning, and in ways that might not be open to me.











The final question I want to pose to you is
a substantive one: Your understanding of critique somehow does relate to
sustaining progress, in a way. Perhaps on the one hand, you are not so
optimistic as Weber was, but on the other hand, your work conveys the sense
that it is possible to bridge the gap between concepts and things. I'm not sure
if it's possible, but perhaps you can relate it to the substantive example of
how your work relates to concrete political situations. I think the example of
Israel-Palestine comes to mind best.







Again,
I don't think I am as optimistic as that. In my heart of hearts, I desperately
wish this to be the case. To think of the people who were most influential on
my intellectual development—my cohort of fellow grad students at Johns Hopkins
and our teachers, to whom as a group I owe, really, everything in intellectual
terms—I was certainly in the minority view. Most of them were, I think, working
in the Deleuzian vein of making 'theory worthy of the event.' I just don't
believe that's possible; or anyway I think it's really, really, really hard, the work of a generation to tell that
story well and have it percolate out into our discipline and our culture. In
the meantime, we must muddle through. I hope I'm wrong and I hope they're
right. I'm rooting for them, even as I try to give them a hard time—just as I
give Keohane (Theory Talk #9)
and Waltz and Wendt and everyone else I write about a hard time. But I'd be happy, very happy, to
be wrong.







What I
do think can be done is that you can sustain an awareness of the space between
things-in-themselves and concepts, and by extension some sense of the fragility
and the tenuousness of the things that you think and their links to the things
that you do. Out of this emerges a kind of chastened political praxis.







You mentioned
Israel and Palestine, which I care a great deal about and am trying to address
more squarely in the work I'm doing now, partly on my own and partly in pieces I've
worked on with my colleague Daniel Monk. What we observe is that though the diplomatic
negotiations failed pretty badly twelve and a half years ago, we're still
looking at the same people running the show: the same principal advisers and
discussants and interlocutors: in the US and Israel and in the Palestinian Authority.
The same concepts and assumptions too. Just a few days ago, Dennis Ross
published a long op-ed about how we get the peace process back on track, and
you might think that you're reading something from another time—as though the
conflict were a technical challenge rather than a political one. You know that
Prince song about 'partying like it's 1999'?







I don't
know what a peaceful, enriching, meaningful Israeli-Jewish-Arab-Palestinian-Muslim-Christian
collective co-existence or sharing of space or world looks like, but I know
that this pseudo-politics ain't that. When I see something that's just a
re-hashing, I can say, 'come on guys, that is not thinking, that's recycling
the old stuff and swapping out dates, proper nouns and a few of the verbs.' Nor
is it listening to other voices who might inspire us in different ways, or
might help us rethink our interests, categories and beliefs. Lately, I've been
listening to a band called System Ali, hip-hop guys from Jaffa's Ajami quarter,
who sing in four languages. What they say matters less to me than the fact that
they really seem to like another, they trust each other, they let each voice
sing its song and use its words. They have something to teach me about
listening, thinking, acting and feeling—because it's music after all—and that
can produce its own political openings.







Of course,
there are pressure groups, from industry and AIPAC to
whatever else in the US, and those groups merit discussion and debate, but I'm
also wary of the counter-assumption which follows from folks who talk about
this too reductively: that there actually is an American interest, or a
European or Arab or Israeli one, which somehow transcends partisan interest—one
that can be recovered once the diaspora Jews, the oil moguls, the arms dealers
or the Christian 'Left Behind' people are taken out of the picture. That feels
like the same heady brew that Treitschke and Meinecke and the German realpolitik scholars poured and drank:
that the national state has some transcendent purpose to which we gain access
by rising above or tuning out the voices of the polity or its chattering
classes. Only with a light liberal-internationalist gloss: Meinecke meets David
Lake (Theory Talk # 46),
Anne-Marie Slaughter or John Ikenberry.







I can
also go meet starry-eyed idealists who want to hold hands and sing John Lennon,
I can say to them yes, I want to hold your hand and sing John Lennon, but I am
also enough of a social scientist to know that if a policy does not respond to
real and pressing problems—water, land, borders etc.—that any approach that
does not respond to those things will be hopelessly idealist. It will be what
my granny called luftmentsch-nachess—the
silly imaginings of men with their heads in the clouds, like the parable about Thales
and the Thracian maiden. I am not interested in being either a luftmentsch nor a technocrat. So what
does that leave with you with? You need to balance.







You can
look at groups at the margins of political culture to see what they can tell
you. In Israel and Palestine, it's groups like Ta'ayush, Breaking the Silence and Zochrot, and this settler
leader who recently died, Rabbi Frohman, who was going out and meeting every
Palestinian leader he could because for him, being a Jew in the land was not,
in the first instance about his Israeli passport. There were and are
possibilities for discussion that feel really pregnant and feel very different
from the conversation we are sustaining now; which reveal its shallowness and
its limitations and its pretentiousness. These other voices are of course not
ideal either, they are going to have their own problems and limitations, their
own descent into power and exclusion and so on, but they reveal some of the lie
of what we're doing now.







I guess
in the end, social scientists make a living imagining the future on the basis
of the past. I also spend a lot of time reading novels and watching books and
films. Partly because I am lazy and I like them. Partly because I'm looking for
those novels and films to help me imagine other possibilities of being that
aren't drawn from the past. Art, Dewey tells us in The Public and its Problems,
is the real bearer of newness. Maybe then, I get to grab onto those things and
say ok, what if we made those them responsive to an expansive materialist
analysis of what an Israeli-Palestinian peace would need to survive? What if we
held the luftmentsch's feet to the
materialist/pragmatic fire, even as we held the wonk's feet to the luftmentsch's fire? Let them both squeal
for a while. There's possibility there.







Daniel J. Levine is assistant professor at the University of Alabama. Among his recent publications (see below) stands out his book Recovering International Relations.



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Related links








Faculty Profile at U-Alabama
Read the first chapter of Levine's Recovering IR (2012) here (pdf)
Read Barder and Levine's The World is Too Much (Millennium, 2012) here (pdf)
Read Levine's Why Morgenthau was not a Critical Theorist (International Relations, 2013) here (pdf)
Read Monk and Levine's The Resounding Silence here (pdf)




Print version of this Talk (pdf)

BACKGROUND:Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. METHODS:Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. FINDINGS:Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2-47·5) in 1990 to 60·3 (58·7-61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9-3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6-421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0-3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5-1040·3]) residing in south Asia. INTERPRETATION:The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC. FUNDING:Bill & Melinda Gates Foundation.

Publisher's version (útgefin grein) ; Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (>= 65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2.5th and 97.5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45.8 (95% uncertainty interval 44.2-47.5) in 1990 to 60.3 (58.7-61.9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2.6% [1.9-3.3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0.79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388.9 million (358.6-421.3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3.1 billion (3.0-3.2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968.1 million [903.5-1040.3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC. ; Lucas Guimaraes Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (Capes) -Finance Code 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). Olatunji O Adetokunboh acknowledges South African Department of Science & Innovation, and National Research Foundation. Anurag Agrawal acknowledges support from the Wellcome Trust DBT India Alliance Senior Fellowship IA/CPHS/14/1/501489. Rufus Olusola Akinyemi acknowledges Grant U01HG010273 from the National Institutes of Health (NIH) as part of the H3Africa Consortium. Rufus Olusola Akinyemi is further supported by the FLAIR fellowship funded by the UK Royal Society and the African Academy of Sciences. Syed Mohamed Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. Marcel Ausloos, Claudiu Herteliu, and Adrian Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDSUEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Till Winfried Barnighausen acknowledges support from the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. Juan J Carrero was supported by the Swedish Research Council (2019-01059). Felix Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. Vera Marisa Costa acknowledges support from grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundacao para a Ciencia e a Tecnologia (FCT), IP, under the Norma TransitA3ria DL57/2016/CP1334/CT0006. Jan-Walter De Neve acknowledges support from the Alexander von Humboldt Foundation. Kebede Deribe acknowledges support by Wellcome Trust grant number 201900/Z/16/Z as part of his International Intermediate Fellowship. Claudiu Herteliu acknowledges partial support by a grant co-funded by European Fund for Regional Development through Operational Program for Competitiveness, Project ID P_40_382. Praveen Hoogar acknowledges the Centre for Bio Cultural Studies (CBiCS), Manipal Academy of Higher Education(MAHE), Manipal and Centre for Holistic Development and Research (CHDR), Kalghatgi. Bing-Fang Hwang acknowledges support from China Medical University (CMU108-MF-95), Taichung, Taiwan. Mihajlo Jakovljevic acknowledges the Serbian part of this GBD contribution was co-funded through the Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. Aruna M Kamath acknowledges funding from the National Institutes of Health T32 grant (T32GM086270). Srinivasa Vittal Katikireddi acknowledges funding from the Medical Research Council (MC_UU_12017/13 & MC_UU_12017/15), Scottish Government Chief Scientist Office (SPHSU13 & SPHSU15) and an NRS Senior Clinical Fellowship (SCAF/15/02). Yun Jin Kim acknowledges support from the Research Management Centre, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/0001). Kewal Krishan acknowledges support from the DST PURSE grant and UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. Manasi Kumar acknowledges support from K43 TW010716 Fogarty International Center/NIMH. Ben Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. Ivan Landires is a member of the Sistema Nacional de InvestigaciA3n (SNI), which is supported by the Secretaria Nacional de Ciencia Tecnologia e Innovacion (SENACYT), Panama. Jeffrey V Lazarus acknowledges support by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union [CP18/00074]). Peter T N Memiah acknowledges CODESRIA; HISTP. Subas Neupane acknowledges partial support from the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital. Shuhei Nomura acknowledges support from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). Alberto Ortiz acknowledges support by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. George C Patton acknowledges support from a National Health & Medical Research Council Fellowship. Marina Pinheiro acknowledges support from FCT for funding through program DL 57/2016 -Norma transitA3ria. Alberto Raggi, David Sattin, and Silvia Schiavolin acknowledge support by a grant from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4 -Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). Daniel Cury Ribeiro acknowledges support from the Sir Charles Hercus Health Research Fellowship -Health Research Council of New Zealand (18/111). Perminder S Sachdev acknowledges funding from the NHMRC Australia. Abdallah M Samy acknowledges support from a fellowship from the Egyptian Fulbright Mission Program. Milena M Santric-Milicevic acknowledges support from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract No. 175087). Rodrigo Sarmiento-Suarez acknowledges institutional support from University of Applied and Environmental Sciences in Bogota, Colombia, and Carlos III Institute of Health in Madrid, Spain. Maria Ines Schmidt acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. Sheikh Mohammed Shariful Islam acknowledges a fellowship from the National Heart Foundation of Australia and Deakin University. Aziz Sheikh acknowledges support from Health Data Research UK. Kenji Shibuya acknowledges Japan Ministry of Education, Culture, Sports, Science and Technology. Joan B Soriano acknowledges support by Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Rafael Tabares-Seisdedos acknowledges partial support from grant PI17/00719 from ISCIII-FEDER. Santosh Kumar Tadakamadla acknowledges support from the National Health and Medical Research Council Early Career Fellowship, Australia. Marcello Tonelli acknowledges the David Freeze Chair in Health Services Research at the University of Calgary, AB, Canada. ; "Peer Reviewed"